Diaminopyrimidine derivatives and processes for the preparation thereof

ABSTRACT

The present invention provides a diaminopyrimidine derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof. The diaminopyrimidine derivative or its pharmaceutically acceptable salt functions as a 5-HT 4  receptor agonist, and therefore can be usefully applied for preventing or treating dysfunction in gastrointestinal motility, one of the gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony.

CROSS-REFERENCE TO PRIOR APPLICATIONS

This is a Divisional Application of U.S. patent application Ser. No.14/001,489, filed on Aug. 23, 2013, which was a National PhaseApplication filed under 35 U.S.C. § 371 as a national stage ofPCT/KR2012/001427, filed on Feb. 24, 2012, an application claiming thebenefit under 35 U.S.C. § 119 of the Korean Application No.10-2011-0016981, filed on Feb. 25, 2011 the content of each of which ishereby incorporated by reference in their entirety.

TECHNICAL FIELD

The present invention relates to a novel 5-HT₄ receptor agonist, morespecifically a novel diaminopyrimidine derivative or itspharmaceutically acceptable salt having an activity as a 5-HT₄ receptoragonist, a process for the preparation thereof, a pharmaceuticalcomposition comprising the same, and a use thereof.

BACKGROUND ART

Serotonin (5-hydroxytryptamine, 5-HT), one of the neurotransmitters, isbroadly distributed throughout human body including both the centralnervous system and the peripheral nervous system. Approximately 95% ofthe human body's total serotonin is found in the gastrointestinal tract,while about 5% thereof is found in the brain. Serotonin receptors arelocated in intestinal nerves, enterochromaffin cells, intestinal smoothmuscle, immune tissues, etc. Serotonin receptor subtypes include 5-HT₁,5-HT₂, 5-HT₃, 5-HT₄, 5-HT₅, 5-HT₆, and 5-HT₇. Interactions between thesevarious receptors and serotonin are linked to various physiologicalfunctions. Therefore, various researches have been performed fordeveloping therapeutic agents that are capable of interacting with aspecific serotonin subtype as a target. The researches includeidentification of 5-HT₄ receptors and active agents interactingtherewith (Langlois and Fischmeister, J. Med. Chem. 2003, 46, 319-344).

It has been found by the previous literatures that 5-HT₄ receptoragonists are useful for treating an abnormal gastrointestinal motility,i.e., dysfunction in gastrointestinal motility. The abnormalgastrointestinal motility may result in various disorders, for exampleirritable bowel syndrome (IBS), constipation, dyspepsia, delayed gastricemptying, gastroesophageal reflux disease (GERD), gastroparesis,post-operative ileus, intestinal pseudo-obstruction, drug-induceddelayed transit, etc.

Representative 5-HT₄ receptor agonists disclosed in prior arts includetegaserod (an aminoguanidine derivative, U.S. Pat. No. 5,510,353),prucalopride (a benzofuran carboxamide derivative, EP0445862), cisapride(a benzamide derivative, U.S. Pat. No. 4,962,115), mosapride(EP0243959), etc. These compounds are known as an agent stimulatinggastrointestinal motility.

DETAILED DESCRIPTION OF THE INVENTION Technical Problem

The present inventors found that a certain diaminopyrimidine derivativefunctions as a 5-HT₄ receptor agonist, and therefore can be usefullyapplied for preventing or treating dysfunction in gastrointestinalmotility.

Therefore, the present invention provides the above diaminopyrimidinederivative or its pharmaceutically acceptable salt, a process for thepreparation thereof, a pharmaceutical composition comprising the same,and a use thereof.

Technical Solution

According to an aspect of the present invention, there is provided a useof a diaminopyrimidine derivative or its pharmaceutically acceptablesalt for the manufacture of a medicament for preventing or treating adysfunction in gastrointestinal motility

According to another aspect of the present invention, there is provideda pharmaceutical composition for preventing or treating a dysfunction ingastrointestinal motility comprising a diaminopyrimidine derivative orits pharmaceutically acceptable salt as an active ingredient.

According to still another aspect of the present invention, there isprovided a diaminopyrimidine derivative or its pharmaceuticallyacceptable salt.

According to still another aspect of the present invention, there isprovided a process for preparing the diaminopyrimidine derivative or itspharmaceutically acceptable salt.

Advantageous Effects

The compound of the present invention, i.e., the diaminopyrimidinederivative or its pharmaceutically acceptable salt, functions as a 5-HT₄receptor agonist, and therefore can be usefully applied for preventingor treating dysfunction in gastrointestinal motility, one of thegastrointestinal diseases, such as gastroesophageal reflux disease(GERD), constipation, irritable bowel syndrome (IBS), dyspepsia,post-operative ileus, delayed gastric emptying, gastroparesis,intestinal pseudo-obstruction, drug-induced delayed transit, or diabeticgastric atony.

BEST MODE FOR CARRYING OUT THE INVENTION

As used herein, the term “alkyl” refers to a straight or branchedaliphatic hydrocarbon radical. For example, C₁-C₆ alkyl means a straightor branched aliphatic hydrocarbon having 1 to 6 carbon atoms, such asmethyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl,sec-butyl, tert-butyl, neopentyl, and isopentyl.

The term “alkoxy or alkyloxy” refers to a radical formed by substitutingthe hydrogen atom of a hydroxyl group with an alkyl. For example, C₁-C₆alkoxy includes methoxy, ethoxy, propoxy, n-butoxy, n-pentyloxy,isopropoxy, sec-butoxy, tert-butoxy, neopentyloxy, and isopentyloxy.

The term “alkenyl” refers to a straight or branched aliphatichydrocarbon radical having one or more double bond(s). For example,C₂-C₆ alkenyl includes ethenyl, propenyl, butenyl, pentenyl, andhexenyl.

The term “alkynyl” refers to a straight or branched aliphatichydrocarbon radical having one or more triple bond(s). For example,C₂-C₆ alkynyl includes ethynyl, propynyl, butynyl, pentynyl, andhexynyl.

The present invention provides a use of a compound of Formula 1 or itspharmaceutically acceptable salt for the manufacture of a medicament forpreventing or treating a dysfunction in gastrointestinal motility:

wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-, 3-dionyl,dihydrobenzoimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or anoxo(═O) group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group;a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of amino, C₁₋₅alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a groupselected from the group consisting of the following Formulas A to E(where * in Formulas A to E represents the position attached to thecompounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionallysubstituted with hydroxy,

R₅ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl,pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl,furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl isoptionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, andbenzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionallysubstituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionallysubstituted with phenyl; a trifluoromethyl group; a trifluoroethylgroup; or a phenyl group optionally substituted with halogen,

R₇ is hydrogen; or a C₁₋₅ alkyl group,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.

In the use for the manufacture of a medicament for preventing ortreating a dysfunction in gastrointestinal motility according to thepresent invention, the dysfunction in gastrointestinal motility includesgastrointestinal diseases, such as gastroesophageal reflux disease(GERD), constipation, irritable bowel syndrome (IBS), dyspepsia,post-operative ileus, delayed gastric emptying, gastroparesis,intestinal pseudo-obstruction, drug-induced delayed transit, or diabeticgastric atony. The constipation includes chronic constipation, chronicidiopathic constipation (CIC), opioid-induced constipation (OIC), etc.And also, the dyspepsia includes functional dyspepsia.

In the use for the manufacture of a medicament for preventing ortreating a dysfunction in gastrointestinal motility according to thepresent invention, the compound or its salt may be the compound ofFormula 1 or its pharmaceutically acceptable salt wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or aheteroaryl group selected from the group consisting of quinolinyl,chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of C₁₋₅ alkyl (where theC₁₋₅ alkyl is optionally substituted with halogen) and acetyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, andhydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionallysubstituted with a substituent selected from the group consisting ofamino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or agroup selected from the group consisting of the Formulas A, B, D and E,

R₄ is hydrogen,

R₅ is a C₁₋₅ alkyl group,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl,piperazinyl (where the piperazinyl is optionally substituted withbenzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group;a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; aC₁₋₁₀ alkenyl group optionally substituted with phenyl; atrifluoromethyl group; a trifluoroethyl group; or a phenyl groupoptionally substituted with halogen,

R₇ is hydrogen,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, and benzyloxy; a piperidinyl group optionallysubstituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; anazetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety isoptionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.

The present invention also provides a pharmaceutical composition forpreventing or treating a dysfunction in gastrointestinal motilitycomprising a therapeutically effective amount of a compound of Formula 1or its pharmaceutically acceptable salt; and a pharmaceuticallyacceptable carrier

wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or anoxo(═O) group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group;a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of amino, C₁₋₅alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a groupselected from the group consisting of the following Formulas A to E(where * in Formulas A to E represents the position attached to thecompounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionallysubstituted with hydroxy,

R₅ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl,pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl,furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl isoptionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, andbenzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionallysubstituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionallysubstituted with phenyl; a trifluoromethyl group; a trifluoroethylgroup; or a phenyl group optionally substituted with halogen,

R₇ is hydrogen; or a C₁₋₅ alkyl group,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.

In the pharmaceutical composition according to the present invention,the dysfunction in gastrointestinal motility includes gastrointestinaldiseases, such as gastroesophageal reflux disease (GERD), constipation,irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayedgastric emptying, gastroparesis, intestinal pseudo-obstruction,drug-induced delayed transit, or diabetic gastric atony. Theconstipation includes chronic constipation, chronic idiopathicconstipation (CIC), opioid-induced constipation (OIC), etc. And also,the dyspepsia includes functional dyspepsia.

In the pharmaceutical composition according to the present invention,the compound or its salt may be the compound of Formula 1 or itspharmaceutically acceptable salt wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or aheteroaryl group selected from the group consisting of quinolinyl,chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of C₁₋₅ alkyl (where theC₁₋₅ alkyl is optionally substituted with halogen) and acetyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxyl and C₁₋₅alkoxy, benzylamino (where the benzylamino is optionally substitutedwith halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, andhydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionallysubstituted with a substituent selected from the group consisting ofamino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or agroup selected from the group consisting of the Formulas A, B, D and E,

R₄ is hydrogen,

R₅ is a C₁₋₅ alkyl group,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl,piperazinyl (where the piperazinyl is optionally substituted withbenzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group;a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; aC₁₋₁₀ alkenyl group optionally substituted with phenyl; atrifluoromethyl group; a trifluoroethyl group; or a phenyl groupoptionally substituted with halogen,

R₇ is hydrogen,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, and benzyloxy; a piperdinyl group optionallysubstituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; anazetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety isoptionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.

The pharmaceutical composition of the present invention may comprise apharmaceutically acceptable carrier, such as diluents, disintegrants,sweeteners, lubricants, or flavoring agents. The pharmaceuticalcomposition may be formulated to an oral dosage form such as tablets,capsules, powders, granules, suspensions, emulsions, or syrups; or aparenteral dosage form such as injection. The dosage form may be variousforms, e.g., dosage forms for single administration or for multipleadministrations.

The pharmaceutical composition of the present invention may comprise,for example, a diluent (e.g., lactose, corn starch, etc), a lubricant(e.g., magnesium stearate), an emulsifying agent, a suspending agent, astabilizer, and/or an isotonic agent. If necessary, the compositionfurther comprises sweeteners and/or flavoring agents.

The composition of the present invention may be administered orally orparenterally, including intravenous, intraperitoneal, subcutaneous,rectal and topical routes of administration. Therefore, the compositionof the present invention may be formulated into various forms such astablets, capsules, aqueous solutions or suspensions. In the case oftablets for oral administration, carriers such as lactose, corn starch,and lubricating agents, e.g. magnesium stearate, are conventionallyused. In the case of capsules for oral administration, lactose and/ordried corn starch can be used as a diluent. When an aqueous suspensionis required for oral administration, the active ingredient may becombined with emulsifying and/or suspending agents. If desired, certainsweetening and/or flavoring agents may be used. For intramuscular,intraperitoneal, subcutaneous and intravenous administration, sterilesolutions of the active ingredient are usually prepared, and the pH ofthe solutions should be suitably adjusted and buffered. For intravenousadministration, the total concentration of solutes should be controlledin order to render the preparation isotonic. The composition of thepresent invention may be in the form of an aqueous solution containingpharmaceutically acceptable carriers, e.g., saline having a pH level of7.4. The solutions may be introduced into a patient's intramuscularblood-stream by local bolus injection.

The compound of Formula 1 or its pharmaceutically acceptable salt may beadministered in a therapeutically effective amount ranging from about0.001 mg/kg to about 10 mg/kg per day to a subject patient. Of course,the dosage may be changed according to the patients age, weight,susceptibility, symptom, or activity of the compound.

The present invention also provides a method for treating a dysfunctionin gastrointestinal motility, such as gastroesophageal reflux disease(GERD), constipation, irritable bowel syndrome (IBS), dyspepsia,post-operative ileus, delayed gastric emptying, gastroparesis,intestinal pseudo-obstruction, drug-induced delayed transit, or diabeticgastric atony, in a patient, which comprises administering atherapeutically effective amount of the compound of Formula 1 or itspharmaceutically acceptable salt to the patient in need thereof. Theconstipation includes chronic constipation, chronic idiopathicconstipation (CIC), opioid-induced constipation (OIC), etc. And also,the dyspepsia includes functional dyspepsia.

The present invention also provides a compound of Formula 1 or itspharmaceutically acceptable salt:

wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or

a heteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-, 3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or anoxo(═O) group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; a phenoxy group;a benzyloxy group; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of amino, C₁₋₅alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or a groupselected from the group consisting of the following Formulas A to E(where * in Formulas A to E represents the position attached to thecompounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionallysubstituted with hydroxy,

R₅ is a C₁₋₅ alkyl group optionally substituted with phenyl; or a C₂₋₆alkenyl group optionally substituted with phenyl or C₃₋₆ cycloalkyl,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, pyrimidinyl,pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, thiazolyl,furanyl, pyrrolyl, piperidinyl, piperazinyl (where the piperazinyl isoptionally substituted with benzyl), C₃₋₆ cycloalkyl, acetyl, andbenzoyl; a C₃₋₆ cycloalkyl group; a piperidinyl group optionallysubstituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenyl group optionallysubstituted with phenyl; a trifluoromethyl group; a trifluoroethylgroup; or a phenyl group optionally substituted with halogen,

R₇ is hydrogen; or a C₁₋₅ alkyl group,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.

Preferably, the compound or its salt may be the compound of Formula 1 orits pharmaceutically acceptable salt wherein,

R₁ is a phenyl group substituted with one or more substituents selectedfrom the group consisting of hydroxy, amino, halogen, cyano, nitro,hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or aheteroaryl group selected from the group consisting of quinolinyl,chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of C₁₋₅ alkyl (where theC₁₋₅ alkyl is optionally substituted with halogen) and acetyl,

R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxyl and C₁₋₅alkoxy, benzylamino (where the benzylamino is optionally substitutedwith halogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, andhydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group,

R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionallysubstituted with a substituent selected from the group consisting ofamino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or agroup selected from the group consisting of the Formulas A, B, D and E.

R₄ is hydrogen,

R₅ is a C₁₋₅ alkyl group,

R₆ is a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxy, halogen, C₁₋₅ alkoxy,amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono- ordi-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl,piperazinyl (where the piperazinyl is optionally substituted withbenzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group;a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; aC₁₋₁₀ alkenyl group optionally substituted with phenyl; atrifluoromethyl group; a trifluoroethyl group; or a phenyl groupoptionally substituted with halogen,

R₇ is hydrogen,

R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, and benzyloxy; a piperidinyl group optionallysubstituted with benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; anazetidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety isoptionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.

The compound of Formula 1 or its pharmaceutically acceptable salt mayhave substituents containing asymmetric carbon and therefore be in theform of racemic mixture (RS) or in forms of optical isomers, such as (R)or (S) isomer. The compound of Formula 1 or its pharmaceuticallyacceptable salt comprises both racemic mixture (RS) and optical isomerssuch as (R) or (S) isomer. And also, the compound of Formula 1 or itspharmaceutically acceptable salt may be in the form of cis- ortrans-geometrical isomer, according to substituents having e.g., thedouble bond therein. The compound of Formula 1 or its pharmaceuticallyacceptable salt comprises both cis- and trans-geometrical isomers. Andalso, the compound of Formula 1 or its pharmaceutically acceptable saltmay be in the form of one or more diastereomic isomer(s) or a mixturethereof. The compound of Formula 1 or its pharmaceutically acceptablesalt comprises both diastereomic isomer(s) and a mixture thereof.

The compound of Formula 1 of the present invention may be in apharmaceutically acceptable salt form. The salt may be an acid additionsalt form, which includes e.g., salts derived from an inorganic acidsuch as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfonicacid, sulfamic acid, phosphoric acid, or nitric acid; and salts derivedfrom an organic acid such as acetic acid, propionic acid, succinic acid,glycolic acid, stearic acid, citric acid, maleic acid, malonic acid,methanesulfonic acid, ethanesulfonic acid, tartaric acid, hydroxymaleicacid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid,2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid,benzenesulfonic acid, oxalic acid or trifluoroacetic acid. The salt maybe prepared by reacting a compound of Formula 1 in the form of free basewith a salt-forming inorganic or organic acid in stoichiometric amountor excessive amount, in a suitable solvent or a mixture of two or moresolvents.

In the use, the pharmaceutical composition, the treatment method, andthe compound according to the present invention, more preferablecompounds include a compound (or its pharmaceutically acceptable salt)selected from the group consisting of:

-   N-(4-fluorophenyl)-4-propyl-6-(pyrrolidin-1-yl)pyrimidin-2-amine;-   (S)-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ol;-   (R)-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   {1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   N-(4-fluorophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine;-   (S)—N-(4-fluorophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (R)—N-(4-fluorophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)-1-[2-(4-fluorophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-2-carboxamide;-   N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (R)—N-{1-[2-(4-fluorophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-3-yl}acetamide;-   2,2,2-trifluoro-N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   4-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   4-[3-(dimethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyimidin-2-amine;-   (S)—N-(4-fluorophenyl)-4-propyl-6-[2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]pyrimidin-2-amine;-   (S)—N-(4-fluorophenyl)-4-{2-[(phenylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-amine;-   (S)—N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-4-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   (S)-tert-butyl    1-[2-(4-fluorophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-3-ylcarbamate;-   4-(3-aminopyrrolidin-1-yl)-N-(4-fluorophenyl)-6-propylpyimidin-2-amine;-   4-[3-(diethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;-   (S)—N-(4-fluorophenyl)-4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-N-methylacetamide;-   (S)-1-[2-(4-fluorophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-3-ol;-   (S)—N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyimidin-2-yl}-1H-indol-6-amine;-   (S)—N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyimidin-2-yl}-1H-indol-5-amine;-   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(4-methoxyphenyl)-6-propylpyrimidin-2-amine;-   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(3-methoxyphenyl)-6-propylpyrimidin-2-amine;-   (S)—N-(3-chlorophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)—N-(4-fluoro-3-nitrophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)—N-(4-chloro-3-nitrophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)-3-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine;-   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   (S)-7-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-4-methyl-2H-chromen-2-one;-   (S)—N-(5-chloro-2-methylphenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)—N-(3-chloro-4-methylphenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)—N-[4-fluoro-3-(trifluoromethyl)phenyl]-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)—N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;-   (S)-2-fluoro-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-2-amino-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)—N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyimidin-2-yl}-3-nitrobenzene-1,4-diamine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-fluorophenyl)-6-propylpyimidin-2-amine;-   (S)-tert-butyl    1-[2-(3-cyanophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-3-ylcarbamate;-   3-{4-[3-(diethylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   N-{1-[2-(3-cyanophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-3-yl}-N-methylacetamide;-   (S)-3-[4-(3-hydroxypyrrolidin-1-yl)-6-propylpyimidin-2-ylamino]benzonitrile;-   (R)-3-[4-(2-methylpyrrolidin-1-yl)-6-propylpyimidin-2-ylamino]benzonitrile;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-3-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (R)-tert-butyl    {1-[2-(3-cyanophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-3-yl}methylcarbamate;-   (R)-3-[4-(3-hydroxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (S)-3-[4-(3-methoxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   3-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyimidin-2-ylamino]benzonitrile;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}butyramide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}cyclopentanecarboxamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-(piperidin-1-yl)propanamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}benzamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-fluorobenzamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-phenylacetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(4-fluorophenyl)acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-phenoxypropanamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-isobutoxypropanamide;-   (S)-2-(4-benzylpiperazin-1-yl)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(piperidin-1-yl)acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-oxo-4-phenylbutanamide;-   (S)-2-(4-aminophenyl)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-cyclopentylacetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-methoxyacetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-2-yl)acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-3-yl)acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-4-yl)acetamide;-   (S,E)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-phenylbut-3-enamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(thiophen-2-yl)acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}isobutyramide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl)}3,3,3-trifluoropropanamide;-   3-[4-(2-oxopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (S)-3-{4-[3-(hexylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-propyl-6-[3-(propylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(cyclohexylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(benzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(phenethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(3-phenylpropylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(3-fluorobenzylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(4-hydroxybenzylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(4-ethylbenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(isopentylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(pentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   3-{4-[(3S)-3-(2-methylbutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(isobutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(4-methoxybenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(4-fluorobenzylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-(4-{3-[bis(cyclopropylmethyl)amino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile;-   (S)-3-{4-propyl-6-[3-(pyridin-2-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-propyl-6-[3-(pyridin-3-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-propyl-6-[3-(pyridin-4-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(2-ethylbutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(neopentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(2-fluorobenzylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-(4-propyl-6-{3-[3-(trifluoromethyl)benzylamino]pyrrolidin-1-yl}pyrimidin-2-ylamino)benzonitrile;-   (S)-3-(4-propyl-6-{3-[4-(trifluoromethyl)benzylamino]pyrrolidin-1-yl}pyrimidin-2-ylamino)benzonitrile;-   (S)-4-({1-[2-(3-cyanophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-3-ylamino}methyl)phenylacetate;-   (S)-3-(4-{3-[4-(dimethylamino)benzylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile;-   (S)-3-(4-{3-[(1H-pyrrol-2-yl)methylamino]pyrrolidin-1-yl)-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-{4-propyl-6-[3-(thiophen-2-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-propyl-6-[3-(thiophen-3-ylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(dibutylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-(4-{3-bis[3-(methylthio)propyl]aminopyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile;-   (S)-3-{4-[3-(butylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-(4-{3-[3-(methylthio)propylamino]pyrrolidin-1-yl}-6-propylpyimidin-2-ylamino)benzonitrile;-   (S)—N-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-yl}-1H-indol-6-amine;-   (S)—N¹-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}isopropane-2-sulfonamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methanesulfonamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-fluorobenzenesulfonamide;-   3-{4-[(3S)-3-(sec-butylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(pentan-3-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(2,6-dimethylheptan-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(4,4-dimethylpentan-2-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(3-hydroxy-3-methylbutan-2-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(heptan-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(n-hexan-2-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(5-methylhexan-2-ylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(cyclohexylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-tert-butyl    2-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}ethylcarbamate;-   (S)-3-{4-[3-(I-benzylpiperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(isopropylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(1-benzoylpiperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(1-acetylpipendin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(cyclooctylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(cyclobutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(cyclopentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-tert-butyl    3-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}azetidine-1-carboxylate;-   (S)-3-(4-{3-[2-(benzyloxy)ethylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}propionamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}pivalamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2,2-dimethylbutanamide;-   (S,E)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-methylbut-2-enamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}hexanamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-phenylpropanamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(1H-indol-3-yl)acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxy-2-m    ethylpropanamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-3-(4-methoxyphenyl)propanamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-3-(4-hydroxyphenyl)propanamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-oxopentanamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamide;-   (S)-2-benzyloxy-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-phenoxyacetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(dimethylamino)acetamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}3-(dimethylamino)propanamide;-   (S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-dimethylaminobutanamide;-   N—(S)-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-ethoxyacetamide;-   N—(S)-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(2-methoxyethoxy)acetamide;-   (S)-benzyl    2-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}-2-oxoethylcarbamate;-   (S)-tert-butyl    3-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}-3-oxobutylcarbamate;-   (S)-tert-butyl    4-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamoyl}piperidine-1-carboxylate;-   (R)-2-methyl-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)-2-amino-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (S)-2-methyl-5-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-5-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   5-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)—N¹-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;-   (S)—N¹-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}3-nitrobenzene-1,4-diamine;-   (R)-3-{4-[3-(aminomethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-2-fluoro-5-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-2-fluoro-5-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;-   N-(4-fluorophenyl)-4-methyl-6-(pyrrolidin-1-yl)pyrimidin-2-amine;-   (3R,5S)-1-[2-(4-fluorophenyl)-6-propylpyrimidin-4-yl]-5-(hydroxymethyl)pyrrolidin-3-ol;-   (S)-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (R)-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   {1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (R)—N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indol-6-amine;-   N-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;-   (S)-methyl    1-[2-(1H-indol-6-ylamino)-6-propylpyimidin-4-yl]pyrrolidine-2-carboxylate;-   N-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-3-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-(1-{2-[3-(methylthio)phenylamino]-6-propylpyimidin-4-yl}pyrrolidin-2-yl)methanol;-   (S)-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(1H-indol-5-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(1H-benzo[d]imidazol-5-ylamino)-6-propylpyimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-(1-{6-propyl-2-[2-(trifluoromethyl)-1H-benzo[d]imidazol-5-ylamino]pyrimidin-4-yl}pyrrolidin-2-yl)methanol;-   (S)-{1-[2-(4-methoxyphenylamino)-6-propylpyimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(3-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(3-methoxyphenylamino)-6-propylpyimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-(1-{6-propyl-2-[3-(trifluoromethyl)phenylamino]pyrimidin-4-yl}pyrrolidin-2-yl)methanol;-   (S)-{1-[2-(5-chloro-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(5-methoxy-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(3-nitrophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(4-fluor-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[6-propyl-2-(quinolin-6-ylamino)pyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-2-yl)methanol;-   (S)-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-5-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-2-fluoro-5-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-2-amino-5-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-{1-[6-propyl-2-(quinolin-3-ylamino)pyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(indolin-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-3-{4-[3-(aminoethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(piperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-[3-(1-butylpiperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)—N-{1-[6-butyl-2-(3-cyanophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-3-{4-butyl-6-[2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (R)-3-[4-butyl-6-(2-methylpyrrolidin-1-yl)pyrimidin-2-ylamino]benzonitrile;-   (S)-3-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-tert-butyl    1-[6-butyl-2-(3-cyanophenylamino)pyrimidin-4-yl]pyrrolidin-3-ylcarbamate;-   (S)—N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-5-{4-butyl-6-[2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile;-   (R)-5-[4-butyl-6-(2-methylpyrrolidin-1-yl)pyrimidin-2-ylamino]-2-methylbenzonitrile;-   (S)-5-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-tert-butyl    1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]pyrrolidin-3-ylcarbamate;-   (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-butylpyrimidin-2-ylamino]benzonitrile;-   (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   (S)-3-{4-butyl-6-[3-(isopropylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-butyl-6-[3-(diethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-butyl-6-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-5-{4-butyl-6-[3-(isopropylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-{4-butyl-6-[3-(diethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-(4-butyl-6-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino)-2-methylbenzonitrile;-   (S)—N-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-(1-{2-[3-(methylthio)phenylamino]-6-propylpyimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-(1-{6-propyl-2-[3-(trifluoromethyl)phenylamino]pyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-{1-[2-(4-methyl-2-oxo-2H-chromen-7-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-benzyl    5-[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methoxyphenylcarbamate;-   (S)—N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-(1-{2-[4-fluoro-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(5-chloro-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-3-[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzamide;-   (S)-3-{[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}-N-methylbenzamide;-   (S)—N-[1-(2-{[3-(aminomethyl)phenyl]amino}-6-propyl    pyrimidin-4-yl)pyrrolidin-3-yl]acetamide;-   (S)-3-{[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}-4-chlorobenzamide;-   (S)—N-{1-[2-(4-amino-3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{2-[(4-aminophenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{2-[(4-chloro-3-hydroxyphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)-4-{[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}-2-hydroxybenzoic    acid;-   (S)-5-{[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}-2-hydroxybenzoic    acid;-   (S)—N-(1-{2-[(3-hydroxy-4-methyl    phenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{2-[(3-chloro-4-hydroxyphenyl)amino]-6-propylpyimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{2-[(4-hydroxy-3-methyl    phenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{2-[(3-fluoro-4-hydroxyphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{2-[(3-hydroxy-4-methoxyphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{2-[(3-methoxy-4-methylphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-[1-(2-{[4-methyl-3-(trifluoromethyl)phenyl]amino)-6-propylpyrimidin-4-yl}pyrrolidin-3-yl]acetamide;-   (S)—N-(1-{2-[(3,4-dimethylphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{2-[(3-fluoro-4-methylphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-{1-[2-(3-amino-4-methoxyphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide-   N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(3-methoxyphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(5-methoxy-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(4-methoxyphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-(1-{6-propyl-2-[3-(trifluoromethyl)phenylamino]pyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   N-{1-[2-(3-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(5-chloro-2-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-(1-{2-[3-(methylthio)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   N-{1-[2-(1H-indol-5-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-(1-{6-propyl-2-[2-(trifluoromethyl)-1H-benzo[d]imidazol-5-ylamino]pyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   N-{1-[6-propyl-2-(quinolin-6-ylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(4-methyl-2-oxo-2H-chromen-7-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[6-propyl-2-(quinolin-3-ylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(4-amino-3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (R)—N-(4-chloro-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine;-   (R)-4-(2-methylpyrrolidin-1-yl)-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-ylamine;-   (R)—N-[4-(2-methylpyrrolidin-1-yl)-6-propylpyimidin-2-yl]-1H-indol-6-amine;-   (R)-4-(2-methylpyrrolidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   (R)-4-methyl-7-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2H-chromen-2-one;-   (R)—N-(3-chloro-4-methylphenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine;-   (R)-4-(2-methylpyrrolidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-ylamine;-   (R)—N-(4-fluoro-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine;-   (R)—N-(4-methyl-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine;-   (R)—N-[4-fluor-3-(trifluoromethyl)phenyl]-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamine;-   (R)—N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;-   (R)-benzyl    2-methoxy-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]phenylcarbamate;-   (R)-2-fluoro-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (R)—N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;-   (R)-1-{6-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]indolin-1-yl}ethanone;-   (R)—N-(5-chloro-2-methylphenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine;-   (R)-4-methoxy-N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine;-   (R)-4-chloro-N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine;-   (R)-4-fluoro-N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine;-   (R)-4-methyl-N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine;-   (S)-3-{4-[3-(2-hydroxyethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;-   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;-   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-methyl    benzene-1,4-diamine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-chloro-3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine;-   (S)—N-[4-(3-aminopyrrolidin-1-yl)-6-propylpyimidin-2-yl]-1H-indol-6-amine;-   (S)-4-(3-aminopyrrolidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-(5-chloro-2-methyl    phenyl)-6-propylpyrimidin-2-amine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-(3-chloro-4-methyl    phenyl)-6-propylpyimidin-2-amine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;-   (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;-   (S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;-   (S)-2-amino-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (S)-benzyl    5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methoxyphenylcarbamate;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-[3,5-bis(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine;-   (S)-4-(3-aminopyrrolidin-1-yl)-N-(3,    5-dimethoxyphenyl)-6-propylpyrimidin-2-amine;-   (S)-3-amino-5-{[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]amino}benzonitrile;-   (S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzenesulfonamide;-   (S)—N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;-   (S)-4-fluoro-N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;-   (S)—N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-4-methylbenzene-1,3-diamine;-   (S)-4-methoxy-N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;-   (S)—N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyimidin-2-yl}indolin-6-amine;-   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]4-methyl    benzene-1,3-diamine;-   (S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]4-fluorobenzene-1,3-diamine;-   (S)—N-(4-chloro-3-nitrophenyl)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;-   (S)-5-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-fluorobenzonitrile;-   (S)-5-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine;-   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   (S)—N-(5-chloro-2-methylphenyl)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)—N-(3-chloro-4-methylphenyl)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine;-   (S)—N¹-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-yl}-4-methylbenzene-1,3-diamine;-   (S)—N¹-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;-   3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-{1-[6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)—N-{1-[6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-4-ethyl-N-(4-fluorophenyl)-6-(2-methoxymethylpyrrolidin-1-yl)pyrimidin-2-amine;-   4-ethyl-N-(4-fluorophenyl)-6-(2-methylpyrrolidin-1-yl)pyrimidin-2-amine;-   (S)-4-ethyl-6-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)pyrimidin-2-amine;-   (S)-3-[4-(3-phenoxypyrrolidin-1-yl)-6-propylpyimidin-2-ylamino]benzonitrile;-   (S)-2-amino-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;-   (S)-3-[4-(2-formylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;-   (S)-3-(4-{2-[(methylamino)methyl]pyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-3-(4-{2-[(cyclobutylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile;-   (S)-3-(4-{2-[(4-fluorobenzylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile;-   (S)-3-(4-propyl-6-{2-[(propylamino)methyl]pyrrolidin-1-yl}pyrimidin-2-ylamino)benzonitrile;-   (S)-3-(4-{2-[(2-hydroxyethylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile;-   (S)-2-methyl-5-{4-propyl-6-[3-(propylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-2-methyl-5-(4-{3-[3-(methylthio)propylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile;-   (S)-5-(4-{3-[(1H-pyrrol-2-yl)methylamino]pyrrolidin-1-yl}-6-propylpyimidin-2-ylamino)-2-methylbenzonitrile;-   (S)-5-{4-[3-(4-hydroxybenzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;-   (S)-5-{4-[3-(isopropylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-(4-[3-(cyclobutylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-{4-[3-(cyclopentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-5-{4-[3-(cyclohexylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)-2-methyl-5-{4-[3-(pentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-2-methyl-5-{4-[3-(neopentylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;-   (S)-5-(4-{3-[(4,5-dimethylfuran-2-yl)methylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;-   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}propionamide;-   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-phenylacetamide;-   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(piperidin-1-yl)acetamide;-   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-3-yl)    acetamide;-   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-4-yl)acetamide;-   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-(thiophen-2-yl)acetamide;-   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methanesulfonamide;-   (S)-1-(1-{2-[(3-cyano-4-methylphenyl)amino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)-3-ethylurea;-   (R)-3-(4-{3-[(diethylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile;-   (S)—N-{1-[6-butyl-2-(4-methyl-3-nitrophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[6-butyl-2-(4-fluoro-3-nitrophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[6-butyl-2-(4-chloro-3-nitrophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-butylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-butylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-(1-{6-butyl-2-[4-fluoro-3-(trifluoromethyl)phenylamino]pyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)—N-{1-[6-butyl-2-(3-cyano-4-fluorophenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)—N-{1-[2-(4-amino-3-cyanophenylamino)-6-butylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;-   (S)-2-amino-5-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-4-butyl-N-(4-methyl-3-nitrophenyl)-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-amine;-   (S)-4-butyl-N-(4-fluor-3-nitrophenyl)-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-amine;-   (S)-4-butyl-N-(4-chloro-3-nitrophenyl)-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-amine;-   (S)-3-amino-5-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine;-   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;-   (S)-4-butyl-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-amine;-   (S)-5-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-fluorobenzonitrile;-   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-4-fluorobenzene-1,3-diamine;-   (S)—N¹-{4-butyl-6-[3-(methylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-4-chlorobenzene-1,    3-diamine;-   (S)-2-amino-5-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-3-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)-5-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrile;-   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;-   (S)-4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine;-   (S)-4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluoro-3-nitrophenyl)pyrimidin-2-amine;-   (S)-4-butyl-N-(4-chloro-3-nitrophenyl)-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-amine;-   (S)-3-amino-5-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;-   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}5-(trifluoromethyl)benzene-1,3-diamine;-   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}3-(trifluoromethyl)benzene-1,4-diamine;-   (S)-4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]-N-[4-fluoro-3-(trifluoromethyl)phenyl]pyrimidin-2-amine;-   (S)-5-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-fluorobenzonitrile;-   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-4-fluorobenzene-1,3-diamine;-   (S)—N¹-{4-butyl-6-[3-(ethylamino)pyrrolidin-1-yl]pyrimidin-2-yl}-4-chlorobenzene-1,3-diamine;-   (S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-hydroxyacetamide;-   (S)—N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamide;-   (S)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-hydroxyacetamide;-   (S)—N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)-2-hydroxyacetamide;-   (S)—N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)-2-hydroxyacetamide;-   (S)—N-(1-{2-[4-fluoro-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)-2-hydroxyacetamide;-   (S)—N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamide;-   (S)—N-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-hydroxyacetamide;-   (S)—N-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}2-hydroxyacetamide;-   (S)-2-hydroxy-N-(1-{2-[4-methyl-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}pyrrolidin-3-yl)acetamide;-   (S)-4-fluoro-N¹-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;-   (S)-3-amino-5-({4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}amino)benzonitrile;-   (S)-2-amino-5-({4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}amino)benzonitrile;-   (S)—N¹-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine;-   (S)—N¹-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}3-(trifluoromethyl)benzene-1,4-diamine;-   (S)-2-amino-5-({4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyimidin-2-yl}amino)benzonitrile;-   (S)—N-[4-fluoro-3-(trifluoromethyl)phenyl]-4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;-   (S)-4-[3-(ethylamino)pyrrolidin-1-yl]-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine;    and-   (S)—N-(1-{2-[(3,4-diaminophenyl)amino]-6-propylpyimidin-4-yl}pyrrolidin-3-yl)acetamide.

In the use, the pharmaceutical composition, the treatment method, andthe compound according to the present invention, still more preferablecompounds in terms of pharmacological activity include the compound (orits pharmaceutically acceptable salt) described in Table 2-1 to Table2-3.

The present invention includes, within its scope, a process forpreparing a compound of Formula 1 or its pharmaceutically acceptablesalt, which comprises reacting a compound of Formula 2 with a compoundof Formula 3 to obtain a compound of Formula 4; performing a methylationof the compound of Formula 4 to obtain a compound of Formula 5; reactingthe compound of Formula 5 with R₁—NH₂ to obtain a compound of Formula 6;performing a halogenation of the compound of Formula 6 to obtain acompound of Formula 7; and reacting the compound of Formula 7 with acompound of Formula 8 to obtain a compound of Formula 1:

wherein, R₁, R₂, R₃, R₄, and R₅ are the same as defined in the above;and X is halogen.

The compounds of Formula 2 and 3 are commercially available. Thereaction between the compound of Formula 2 and the compound of Formula 3may be performed in the presence of a base and a solvent. The base maybe potassium carbonate, sodium carbonate, etc and the solvent may be anaqueous solvent such as water. Typically, the reaction may be carriedout under heating.

The methylation of the compound of Formula 4 may be carried out using amethylating agent such as iodomethane. The methylation may be performedin the presence of a base and a solvent. The base may be sodiumhydroxide, potassium hydroxide, etc and the solvent may be an aqueoussolvent such as water. Typically, the methylation may be carried out atroom temperature or under heating.

The reaction between the compound of Formula 5 and R₁—NH₂ may beperformed in the absence of a solvent or in the presence of a solventsuch as diglyme. The reaction may be carried out at a temperatureranging from 140° C. to 180° C.

The halogenation of the compound of Formula 6 may be carried out using ahalogenating agent such as phosphorus oxychloride. The halogenation maybe performed preferably at a temperature of about 100° C. or higher. Andalso, for improving reaction rate and/or yield, the halogenation may beperformed in the presence of N,N-dimethylaniline orN,N-dimethylformamide in a catalytic amount.

The reaction between the compound of Formula 7 and the compound ofFormula 8 may be performed in the presence of an organic solvent, suchas anhydrous tetrahydrofuran, alcohol, and 1,4-dioxane. Typically, thereaction may be carried out under heating. And also, for improvingreaction rate and/or yield, the reaction may be performed in thepresence of a metallic catalyst (e.g., palladium), a ligand, and a basesuch as cesium carbonate, triethylamine and diisopropylethylamine; orperformed under microwave ranging from 300 W to 600 W.

The compound of Formula 5 may be also prepared by reacting a compound ofFormula 2 with a compound of Formula 9:

wherein, R₅ is the same as defined in the above.

The compound of Formula 9 is commercially available. The reactionbetween the compound of Formula 2 and the compound of Formula 9 may beperformed in the presence of a base and a solvent. The base may bepotassium carbonate, sodium carbonate, etc and the solvent may be anaqueous solvent such as water. Typically, the reaction may be carriedout at room temperature or under heating.

The compound of Formula 6 may be also prepared by reacting a compound ofFormula 2 with a compound of Formula 10:

wherein, R₁ and R₅ are the same as defined in the above.

The compound of Formula 10 may be easily prepared by using knownmethods, e.g., EP0560726. The reaction between the compound of Formula 2and the compound of Formula 10 may be performed in the presence of abase and a solvent. The base may be sodium methoxide, sodium ethoxide,etc and the solvent may be an alcohol. Typically, the reaction may becarried out under heating.

The present invention also provides a process for preparing a compoundof Formula 1 or its pharmaceutically acceptable salt, which comprisesperforming a halogenation of a compound of Formula 4 to obtain acompound of Formula 11; reacting the compound of Formula 11 with acompound of Formula 8 to obtain a compound of Formula 12; and reactingthe compound of Formula 12 with R₁—NH₂ to obtain a compound of Formula1:

wherein, R₁, R₂, R₃, R₄, and R₅ are the same as defined in the above;and X is halogen.

The halogenation of the compound of Formula 4 may be carried out using ahalogenating agent such as phosphorus oxychloride. The halogenation maybe performed preferably at a temperature of about 100° C. or higher. Andalso, for improving reaction rate and/or yield, the halogenation may beperformed in the presence of N,N-dimethylaniline orN,N-dimethylformamide in a catalytic amount.

The reaction between the compound of Formula 11 and the compound ofFormula 8 may be performed in the presence of an organic solvent, suchas anhydrous tetrahydrofuran, alcohol, chloroform, andN,N-dimethylformamide. Typically, the reaction may be carried out atroom temperature or under heating. And also, for improving reaction rateand/or yield, the reaction may be performed in the presence of a basesuch as triethylamine and diisopropylethylamine.

The reaction between the compound of Formula 12 and R₁—NH₂ may beperformed in the presence of a solvent such as alcohol, toluene,1,4-dioxane, and N,N-dimethylformamide. The reaction may be carried outunder heating. And also, for improving reaction rate and/or yield, thereaction may be performed in the presence of a metallic catalyst (e.g.,palladium), a ligand, and a base (e.g., cesium carbonate); or performedunder microwave ranging from 300 W to 600 W.

The compound of Formula 11 may be also prepared by reacting a compoundof Formula 5 with an acid to obtain a compound of Formula 13; and thenperforming a halogenation of the compound of Formula 13:

wherein, R₅ and X are the same as defined in the above.

The reaction between the compound of Formula 5 and the acid may beperformed using an organic acid (e.g., acetic acid, etc) and aninorganic acid (e.g. hydrochloric acid, etc). The reaction may beperformed in an aqueous solvent such as water. Typically, the reactionmay be carried out under heating.

The halogenation of the compound of Formula 13 may be carried out usinga halogenating agent such as phosphorus oxychloride. The halogenationmay be performed preferably at a temperature of about 100° C. or higher.And also, for improving reaction rate and/or yield, the halogenation maybe performed in the presence of N,N-dimethylaniline orN,N-dimethylformamide in a catalytic amount.

In accordance with an embodiment of the present invention, there isprovided a process for preparing a compound of Formula 1b or itspharmaceutically acceptable salt, which comprises reacting a compound ofFormula 1a with an organic acid or an acyl halide:

wherein, R₁, R₂, R₄, R₅, R₆, and R₇ are the same as defined in theabove.

The reaction between the compound of Formula 1a and the organic acid maybe performed through amide coupling reaction, using a coupling agentsuch as (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphoniumhexafluorophosphate, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidehydrochloride, and 1-hydroxybenzotriazole hydrate; and a base such asdiisopropylethylamine and triethylamine. The coupling reaction may beperformed in an organic solvent such as dichloromethane, andN,N-dimethylformamide. Typically, the coupling reaction is performed atroom temperature.

And also, the reaction between the compound of Formula 1a and the acylhalide may be performed through amide coupling reaction, using anorganic base (e.g., diisopropylethylamine, triethylamine, etc) or aninorganic base (e.g., sodium hydroxide, etc). The coupling reaction maybe performed in an organic solvent such as dichloromethane or a mixedsolvent of an organic solvent and water. Typically, the couplingreaction is performed at room temperature.

The compound of Formula 1b or its pharmaceutically acceptable salt maybe also prepared by reacting a compound of Formula 12a with an organicacid or an acyl halide to obtain a compound of Formula 12b; and thenreacting the compound of Formula 12b with R₁—NH₂ to obtain a compound ofFormula 1b:

wherein, R₁, R₂, R₄, R₅, R₆, and R₇ are the same as defined in theabove; and X is halogen.

The reaction between the compound of Formula 12a and the organic acidmay be performed through amide coupling reaction, using a coupling agentsuch as (benzotriazol-1-yloxy)-tris-(dimethylamino)phosphoniumhexafluorophosphate, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidehydrochloride, and 1-hydroxybenzotriazole hydrate; and a base such asdiisopropylethylamine or triethylamine. The coupling reaction may beperformed in an organic solvent such as dichloromethane, andN,N-dimethylformamide. Typically, the coupling reaction is performed atroom temperature.

And also, the reaction between the compound of Formula 12a and the acylhalide may be performed through amide coupling reaction, using anorganic base (e.g., diisopropylethylamine, triethylamine, etc) or aninorganic base (e.g., sodium hydroxide, etc). The coupling reaction maybe performed in an organic solvent such as dichloromethane or a mixedsolvent of an organic solvent and water. Typically, the couplingreaction is performed at room temperature.

The reaction between the compound of Formula 12b and R₁—NH₂ may beperformed in an organic solvent such as alcohol, toluene, 1,4-dioxane,and N,N-dimethylformamide, etc. Typically, the reaction may be performedunder heating. And also, for improving reaction rate and/or yield, thereaction may be performed in the presence of a metallic catalyst (e.g.,palladium), a ligand, and a base (e.g., cesium carbonate); or performedunder microwave ranging from 300 W to 600 W.

In accordance with another embodiment of the present invention, there isprovided a process for preparing a compound of Formula 1c or itspharmaceutically acceptable salt, which comprises performing a reductiveamination using an aldehyde or a ketone with respect to a compound ofFormula 1a:

wherein, R₁, R₂, R₄, R₅, R₈, and R₉ are the same as defined in theabove.

The reductive amination may be performed using a reducing agent such assodium borohydride, sodium triacetoxyborohydride, and sodiumcyanoborohydride. The reductive amination may be performed in an organicsolvent (e.g., alcohol) at room temperature or at low temperature (e.g.,at 0° C. or less). And also, for improving reaction rate and/or yield,the reaction may be performed in the presence of acetic acid, etc.

The compound of Formula 1c or its pharmaceutically acceptable salt maybe prepared by introducing an amine-protecting group to a compound ofFormula 12a to obtain a compound of Formula 12c; performing analkylation of the compound of Formula 12c to obtain a compound ofFormula 12d; and reacting a compound of Formula 12d with R₁—NH₂,followed by removing the amine-protecting group:

wherein, R₁, R₂, R₄, R₅, and R₈ are the same as defined in the above; Xis halogen; and R₉ is hydrogen. P is an amine-protecting group such astert-butoxycarbonyl.

The reaction for introducing an amine-protecting group to the compoundof Formula 12a may be performed in an organic solvent such asdichloromethane, chloroform, and 1,4-dioxane at room temperature or atlow temperature (e.g., at 0° C. or less). And also, the reaction may beperformed in the presence of a base such as triethylamine,diisopropylethylamine, and 4-dimethylaminopyridine.

The alkylation of the compound of Formula 12c may be performed using analkyl halide. The alkylation may be performed in the presence of a base(e.g., sodium hydride) in an organic solvent (e.g.,N,N-dimethylformamide). The alkylation may be performed at roomtemperature or under heating.

The reaction between the compounds of Formula 12d and R₁—NH₂ may beperformed in an organic solvent such as alcohol, toluene, 1,4-dioxane,and N,N-dimethylformamide. Typically, the reaction is performed underheating. And also, for improving reaction rate and/or yield, thereaction may be performed in the presence of a metallic catalyst (e.g.,palladium), a ligand, and a base (e.g., cesium carbonate); or performedunder microwave ranging from 300 W to 600 W. The reaction for removingthe amine-protecting group may be performed using an acid (e.g.,hydrochloric acid, trifluoroacetic acid, etc) in an organic solvent suchas ethyl acetate and methanol. Typically, the reaction may be performedat room temperature or at low temperature (e.g., at 0° C. or less).

The compound of Formula 12d may be also prepared by performing areductive amination with respect to a compound of Formula 12a to obtaina compound of Formula 12e; and then introducing an amine-protectinggroup to the compound of Formula 12e:

wherein, R₂, R₄, R₅, and R₈ are the same as defined in the above; X ishalogen; and R₉ is hydrogen. P is an amine-protecting group such astert-butoxycarbonyl.

The reductive amination of the compound of Formula 12a may be performedusing a reducing agent such as sodium borohydride, sodiumtriacetoxyborohydride, and sodium cyanoborohydride. The reductiveamination may be in an organic solvent (e.g., alcohol) at roomtemperature or at low temperature (e.g., at 0° C. or less). And also,for improving reaction rate and/or yield, the reaction may be performedin the presence of acetic acid, etc.

The reaction for introducing an amine-protecting group to the compoundof Formula 12e may be performed in an organic solvent such asdichloromethane, chloroform and 1,4-dioxane at room temperature or atlow temperature (e.g., at 0° C. or less). And also, the reaction may beperformed in the presence of a base such as triethylamine,diisopropylethylamine, and 4-dimethylaminopyridine.

The following examples and experimental examples are provided forillustration purposes only, and are not intended to limit the scope ofthe invention.

Preparation 1. 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine<Step 1>2-(methylthio)-6-propylpyrimidin-4(3H)-one

A mixture of 6-n-propyl-2-thiouracil (25.0 g, 0.15 mol), sodiumhydroxide (5.9 g, 0.15 mol), iodomethane (10.2 ml, 0.17 mol), and water(300 ml) was stirred at room temperature overnight and then filtered.The resulting solid was dried in vacuo to give the titled compound (25.0g) as a white solid. The product was used in the subsequent reactionwithout further purification.

<Step 2>2-(4-fluorophenylamino)-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (3.7 g, 0.02mol) prepared in Step 1 and 4-fluoroaniline (6.7 g, 0.06 mol) wasstirred at 160° C. overnight. The reaction mixture was cooled to roomtemperature, and then ethanol (50 ml) and charcoal (1 g) were addedthereto. The reaction mixture was stirred for 1 hour and then filtered.The filtrate was concentrated under reduced pressure. Ethanol (20 ml)was added to the resulting residue, which was then stirred for 1 hour.The reaction mixture was filtered to give the titled compound as a graysolid.

¹H-NMR (400 MHz, CD₃OD) δ 7.70-7.50 (m, 2H), 7.07 (t, 2H), 5.75 (s, 1H),2.43 (t, 2H), 1.70 (q, 2H), 0.98 (t, 3H)

<Step 3>4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine

2-(4-Fluorophenylamino)-6-propylpyrimidin-4(3H)-one (2.2 g, 8.9 mmol)prepared in Step 2 was added to phosphorus oxychloride (1.5 ml, 16.2mmol), which was then stirred at 110° C. for 5 hours. After cooling toroom temperature, ice water was added to the reaction mixture, which wasthen basified to pH 9 with sodium hydroxide. The aqueous layer wasextracted with ethyl acetate. The resulting organic layer was dried onanhydrous sodium sulfate and then concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(ethyl acetate) to give 2.2 g of the titled compound as a yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 7.65-7.50 (m, 2H), 7.03 (t, 2H), 6.63 (s, 1H),2.60 (t, 2H), 1.75 (q, 2H), 0.99 (t, 3H)

Preparation 2.(S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine<Step 1>2,4-dichloro-6-propylpyrimidine

Phosphorus oxychloride (100 ml) was slowly added at room temperature to6-propyl-2-thiouracil (17.7 g, 0.1 mol), which was then stirred at 110°C. overnight. The reaction mixture was added to ice water and thenneutralized with a saturated aqueous solution of sodium bicarbonate. Thereaction mixture was extracted with dichloromethane. The organic layerwas dried on anhydrous magnesium sulfate, filtered, and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=50/1) togive 10.3 g of the titled compound as pale yellow oil.

¹H-NMR (400 MHz, CDCl₃) δ 7.16 (s, 1H), 2.73 (t, 2H), 1.78 (m, 2H), 0.99(t, 3H)

<Step 2>(S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine

2,4-Dichloro-6-propylpyrimidine (1.4 g, 7.3 mmol) prepared in Step 1 wasdissolved in tetrahydrofuran (15 ml), and then(S)-2-(methoxymethyl)pyrrolidine (1.2 g, 10.4 mmol) was added thereto atroom temperature. The reaction mixture was stirred at 60° C. overnightand then cooled to room temperature. The reaction mixture wasconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=10/1) togive 1.5 g of the titled compound as pale yellow oil. The product wasused in the subsequent reaction without further purification.

Preparation 3. 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile<Step 1>3-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (6.4 g, 34.7mmol) prepared in Step 1 of Preparation 1 and 3-aminobenzonitrile (12.3g, 104.1 mmol) was stirred at 160° C. overnight. The reaction mixturewas cooled to room temperature and then ethanol (50 ml) was addedthereto. The reaction mixture was stirred for 1 hour and then filteredto give 3.5 g of the titled compound as a pale brown solid.

¹H-NMR (400 MHz, CD₃OD) δ8.22 (s, 1H), 7.90-7.80 (m, 1H), 7.55-7.45 (m,1H), 7.45-7.35 (m, 1H), 5.84 (s, 1H), 2.49 (t, 2H), 1.80-1.65 (m, 2H),1.00 (t, 3H)

<Step 2>3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile

3-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile (3.3 g,13.0 mmol) prepared in Step 1 was added to phosphorus oxychloride (10ml). The reaction mixture was stirred at 110° C. for 2 hours and thencooled to room temperature. The reaction mixture was added to ice waterand then basified to pH 9 with sodium hydroxide. The aqueous layer wasextracted with ethyl acetate. The resulting organic layer was dried onanhydrous sodium sulfate and then concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=10/1) to give 3.2 g of the titled compound as ayellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 8.18 (s, 1H), 7.75-7.65 (m, 1H), 7.50-7.20 (m,3H), 6.72 (s, 1H), 2.65 (t, 2H), 1.78 (q, 2H), 1.01 (t, 3H)

Preparation 4. N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine<Step 1>2-(1H-indol-6-ylamino)-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (1 g, 5.43 mmol)prepared in Step 1 of Preparation 1 and 6-aminoindole (789 mg, 5.97mmol) was stirred at 150° C. overnight and then cooled to roomtemperature. The resulting residue was purified with silica gel columnchromatography (dichloromethane/methanol=40/1) to give 1.4 g of thetitled compound as a pale brown solid.

¹H-NMR (400 MHz, CD₃OD) δ 7.81 (s, 1H), 7.51 (d, 1H), 7.21 (d, 1H), 6.95(dd, 1H), 6.42 (d, 1H), 5.70 (s, 1H), 2.44 (dd, 1H), 1.75-1.70 (m, 2H),0.99 (t, 3H).

<Step 2> N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine

A solution of 2-(1H-indol-6-ylamino)-6-propylpyrimidin-4(3H)-one (1.2 g,4.47 mmol) prepared in Step 1, phosphorus oxychloride (822 mg, 5.37mmol), and diisopropylethylamine (1.9 ml, 10.7 mmol) in 1,4-dioxane (45ml) was refluxed under stirring for 30 minutes. The reaction mixture wascooled to room temperature and then concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=4/1) to give 1.1 g of the titled compound as awhite solid.

¹H-NMR (400 MHz, CDCl₃) δ 8.17 (brs, 1H), 8.05 (s, 1H), 7.53 (d, 1H),7.25 (d, 1H), 7.11 (dd, 1H), 6.98 (dd, 1H), 6.58 (s, 1H), 6.48 (s, 1H),2.59 (dd, 2H), 1.81-1.71 (m, 2H), 0.99 (t, 3H).

Preparation 5.(S)-1-(2-chloro-6-propylpyrimidin-4-yl)-N-methylpyrrolidin-3-amine

2,4-Dichloro-6-propylpyrimidine (1 g, 5.2 mmol) prepared in Step 1 ofPreparation 2 was dissolved in ethanol (10 ml) and then(3S)-(−)-3-(methylamino)pyrrolidine (1 g, 10 mmol) was slowly addedthereto at 0° C. The reaction mixture was stirred at room temperatureovernight and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(dichloromethane/methanol=40/1) to give 1 g of the titled compound aspale yellow oil.

¹H-NMR (400 MHz, CDCl₃) δ 6.03 (s, 1H), 3.90-3.30 (m, 5H), 2.52 (t, 2H),2.49 (s, 3H), 2.30-2.15 (m, 1H), 2.10-1.90 (m, 1H), 1.70 (q, 2H), 0.95(t, 3H)

Preparation 6.5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile <Step1>2-methyl-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (5 g, 27.1 mmol)prepared in Step 1 of Preparation 1 and 5-amino-2-methylbenzonitrile (7g, 53 mmol) was stirred at 160° C. overnight. The reaction mixture wascooled to room temperature and then ethanol (30 ml) was added thereto.The reaction mixture was stirred for 1 hour and then filtered to give6.3 g of the titled compound as a pale yellow solid.

¹H-NMR (400 MHz, CD₃OD) δ 8.12 (d, 1H), 7.70-7.60 (m, 1H), 7.35 (d, 1H),5.80 (s, 1H), 2.50-2.40 (m, 5H), 1.73 (q, 2H), 0.99 (t, 3H)

<Step 2>5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile

2-Methyl-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile(6.3 g, 23.5 mmol) prepared in Step 1 was added to phosphorusoxychloride (10 ml). The reaction mixture was stirred at 110 for 2 hoursand then cooled to room temperature. The reaction mixture was added toice water and then basified to pH 9 with sodium hydroxide. The aqueouslayer was extracted with ethyl acetate. The resulting organic layer wasdried on anhydrous sodium sulfate and then concentrated under reducedpressure to give 6 g of the titled compound as a yellow solid. Theproduct was used in the subsequent reaction without furtherpurification.

Preparation 7.N¹-(4-chloro-6-propylpyrimidin-2-yl)-3-nitrobenzene-1,4-diamine

<Step 1>2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (3 g, 16.3 mmol)prepared in Step 1 of Preparation 1 and 2-nitrobenzene-1,4-diamine (5 g,32.6 mmol) was stirred at 160° C. overnight. The reaction mixture wascooled to 70° C. and then ethanol (30 ml) was added thereto. Thereaction mixture was stirred for 1 hour and then filtered to give 4.5 gof the titled compound as a red solid.

¹H-NMR (400 MHz, CD₃OD) δ 8.42 (s, 1H), 7.55-7.45 (m, 1H), 6.96 (d, 1H),5.73 (s, 1H), 2.43 (t, 2H), 1.73 (q, 2H), 0.98 (t, 3H)

<Step 2> N¹-(4-chloro-6-propylpyrimidin-2-yl)-3-nitrobenzene-1,4-diamine

The titled compound (0.4 g) in the form of pale yellow solid wasprepared in accordance with the same procedures as in Step 3 ofPreparation 1, using2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4(3H)-one (4.5 g, 15.5mmol) prepared in Step 1.

¹H-NMR (400 MHz, CDCl₃) δ 8.65 (s, 1H), 7.78 (d, 1H), 7.40 (brs, 1H),7.19 (d, 1H), 6.81 (s, 1H), 2.70 (t, 2H), 1.81 (q, 2H), 1.03 (t, 3H)Preparation 8.5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile

<Step1>2-fluoro-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (8.8 g, 47.8mmol) prepared in Step 1 of Preparation 1 and5-amino-2-fluorobenzonitrile (7.9 g, 57.2 mmol) was stirred at 160° C.overnight. The reaction mixture was cooled to 70° C. and then ethanol(50 ml) was added thereto. The reaction mixture was stirred for 1 hourand then filtered to give 10 g of the titled compound as a pale brownsolid. The product was used in the subsequent reaction without furtherpurification

<Step 2>5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile

The titled compound (10.8 g) in the form of pale brown solid wasprepared in accordance with the same procedures as in Step 3 ofPreparation 1, using2-fluoro-5-(6-oxo-4-propyl-1,6-dihydropyrimidin-2-ylamino)benzonitrile(10 g, 36.7 mmol) prepared in Step 1.

¹H-NMR (400 MHz, CDCl₃) δ 8.20-8.10 (m, 1H), 7.75-7.65 (m, 1H),7.30-7.10 (m, 2H), 6.72 (s, 1H), 2.64 (t, 2H), 1.77 (q, 2H), 1.00 (t,3H)

Preparation 9. 4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine<Step 1>6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-ol

A mixture of ethylpropionyl acetate (1.03 ml, 7.18 mmol),N-(4-fluorophenyl)guanidine (1 g, 6.53 mmol), sodium methoxide (0.39 g,7.18 mmol), and ethanol (30 ml) was refluxed under stirring overnight.The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was dissolvedin water, acidified to pH 4 with a 1N hydrochloric acid solution, andthen filtered. The resulting white solid (0.82 g) was dried in vacuo andthen used in the subsequent reaction without further purification.

<Step 2>4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine

6-Ethyl-2-(4-fluorophenylamino)-pyrimidin-4-ol (0.82 g, 3.52 mmol)prepared in Step 1 was added to phosphorus oxychloride (1.5 ml, 16.2mmol), which was then stirred at 110 for 1 hour. After cooling to roomtemperature, the reaction mixture was added to ice water and thenbasified to pH 9 with potassium hydroxide. The aqueous layer wasextracted with dichloromethane. The resulting organic layer was dried onanhydrous sodium sulfate and then concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(ethyl acetate/n-hexane=2/1) to give 432.2 mg of the titled compound asa white solid.

¹H-NMR (400 MHz, CDCl₃) δ 7.18 (m, 2H), 7.08 (m, 2H), 6.63 (s, 1H), 2.61(m, 2H), 1.23 (t, 3H)

Preparation 10. 4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine<Step 1>2-(4-fluorophenylamino)-6-methylpyrimidin-4-ol

The titled compound (8.2 g) was prepared in accordance with the sameprocedures as in Step 1 of Preparation 9, using ethyl acetoacetate (10g, 76.8 mmol), N-(4-fluorophenyl)guanidine (10.7 g, 69.8 mmol) andsodium methoxide (4.2 g, 71.8 mmol). The product was used in thesubsequent reaction without further purification

<Step 2>4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine

The titled compound (4.5 g) in the form of white solid was prepared inaccordance with the same procedures as in Step 2 of Preparation 9, using2-(4-fluorophenylamino)-6-methylpyrimidin-4-ol (8.2 g, 37.4 mmol)prepared in Step 1 and phosphorus oxychloride (15.9 ml, 172.0 mmol).

¹H-NMR (400 MHz, CDCl₃) δ 7.57-7.54 (m, 2H), 7.21 (brs, 1H), 7.05-7.01(m, 2H), 6.64 (s, 1H), 2.39 (s, 3H)

Preparation 11. 3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile<Step 1>6-butyl-2-(methylthio)pyrimidin-4(3H)-one

A solution of ethyl 3-oxoheptanoate (10 g, 58.1 mmol),2-methyl-2-thiopseudourea sulfate (11.7 g, 63.9 mmol), and sodiumcarbonate (9.8 g, 92.9 mmol) in water (116 ml) was stirred at roomtemperature for 2 days and then filtered. The resulting white solid wasdried in vacuo to give the titled compound (11 g). The product was usedin the subsequent step without further purification.

<Step 2>3-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)benzonitrile

A solution of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (500 mg, 2.52mmol) prepared in Step 1 and 3-aminobenzonitrile (298 mg, 2.52 mmol) inn-butanol (3 ml) was stirred at 170° C. overnight. The reaction mixturewas cooled to room temperature and then purified with silica gel columnchromatography (dichloromethane/methanol=50/1) to give 310 mg of thetitled compound as a brown solid.

¹H-NMR (400 MHz, CDCl₃) δ 9.47 (brs 1H), 8.27 (s, 1H), 7.80 (d, 1H),7.37 (d, 1H), 5.88 (s, 1H), 2.58 (dd, 2H), 1.74-1.70 (m, 2H), 1.46-1.40(m, 2H), 0.98 (t, 3H)

<Step 3>3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile

The titled compound in the form of pale yellow solid was prepared inaccordance with the same procedures as in Step 2 of Preparation 9, using3-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)benzonitrile prepared inStep 2 and phosphorus oxychloride.

¹H-NMR (400 MHz, CDCl₃) δ 8.19 (s, 1H), 7.69 (d, 1H), 7.42 (t, 1H), 7.33(d, 1H), 7.26 (brs, 1H), 6.72 (s, 1H), 2.67 (t, 2H), 1.80-1.65 (m, 2H),1.50-1.30 (m, 2H), 0.97 (t, 3H); (Yield: 80%)

Preparation 12.5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile <Step1>5-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)-2-methylbenzonitrile

A mixture of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (800 mg, 4.03mmol) prepared in Step 1 of Preparation 11 and5-amino-2-methylbenzonitrile (586 mg, 4.44 mmol) was stirred at 170° C.for 6 hours. The reaction mixture was cooled to room temperature andthen purified with silica gel column chromatography(dichloromethane/methanol=100/1) to give 650 mg of the titled compoundas a brown solid.

¹H-NMR (400 MHz, CDCl₃) δ 9.45 (brs 1H), 8.10 (s, 1H), 7.63 (d, 1H),7.25 (d, 1H), 5.78 (s, 1H), 2.55-2.48 (m, 5H), 1.70-1.65 (m, 2H),1.44-1.37 (m, 2H), 0.98 (t, 3H)

<Step 2>5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Step 2 of Preparation 9, using5-(4-butyl-6-oxo-1,6-dihydropyrimidin-2-ylamino)-2-methylbenzonitrileprepared in Step 1 and phosphorus oxychloride.

¹H-NMR (400 MHz, CDCl₃) δ 8.08 (d, 1H), 7.57 (dd, 1H), 7.25 (m, 2H),6.69 (s, 1H), 2.65 (dd, 2H), 2.51 (s, 3H), 1.75-1.68 (m, 2H), 1.45-1.36(m, 2H), 0.96 (t, 3H); (Yield: 85%)

Preparation 13.(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide

A solution of 2,4-dichloro-6-propylpyrimidine (1 g, 5.23 mmol) preparedin Step 1 of Preparation 2, (3S)-(−)-3-acetamidopyrrolidine (1 g, 7.85mmol), and diisopropylethylamine (1.8 ml, 10.46 mmol) in chloroform (52ml) was stirred at 60° C. for 1 hour. The reaction mixture was cooled toroom temperature, washed by water, and then extracted withdichloromethane. The organic layer was dried on anhydrous sodium sulfateand then filtered. The filtrate was concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1) to give 1.2 g of the titled compound as awhite solid.

¹H NMR (400 MHz, CDCl₃) δ 6.52 (brs, 1H), 6.02 (s, 1H), 4.59 (brs, 1H),3.65-3.25 (m, 4H), 2.53 (dd, 2H), 2.28-2.24 (m, 1H), 2.02 (s, 3H),2.02-1.98 (m, 1H), 1.74-1.65 (m, 2H), 0.96 (t, 3H)

Preparation 14.N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide

A solution of 2,4-dichloro-6-propylpyrimidine (200 mg, 1.05 mmol)prepared in Step 1 of Preparation 2, 3-acetamidopyrrolidine (201 mg,1.57 mmol), diisopropylethylamine (0.36 ml, 2.09 mmol) in chloroform(10.5 ml) was stirred at 40° C. for 1 hour. The reaction mixture wascooled to room temperature, washed by water, and then extracted withdichloromethane. The organic layer was dried on anhydrous sodium sulfateand then filtered. The filtrate was concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1) to give 205 mg of the titled compound as awhite solid.

¹H NMR (400 MHz, CDCl₃) δ 6.52 (brs, 1H), 6.02 (s, 1H), 4.59 (brs, 1H),3.65-3.25 (m, 4H), 2.53 (dd, 2H), 2.28-2.24 (m, 1H), 2.02 (s, 3H),2.02-1.98 (m, 1H), 1.74-1.65 (m, 2H), 0.96 (t, 3H)

Preparation 15.(R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine

A solution of 2,4-dichloro-6-propylpyrimidine (1 g, 5.23 mmol) preparedin Step 1 of Preparation 2, (R)-2-methylpyrrolidine (668 mg, 7.85 mmol),diisopropylethylamine (1.8 ml, 10.46 mmol) in chloroform (52 ml) wasstirred at 60° C. for 1 hour. The reaction mixture was cooled to roomtemperature, washed by water, and then extracted with dichloromethane.The organic layer was dried on anhydrous sodium sulfate and thenfiltered. The filtrate was concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=20/1) to give 910 mg of the titled compound ascolorless liquid.

¹H NMR (400 MHz, CDCl₃) δ 6.00 (brs, 1H), 4.44-3.25 (m, 3H), 2.52 (dd,2H), 2.12-1.95 (m, 3H), 1.75-1.66 (m, 3H), 1.22 (d, 3H), 0.96 (t, 3H)

Preparation 16.N¹-(4-butyl-6-chloropyrimidin-2-yl)-3-nitrobenzene-1,4-diamine <Step1>2-(4-amino-3-nitrophenylamino)-6-butylpyrimidin-4(3H)-one

The titled compound in the form of yellow solid was prepared inaccordance with the same procedures as in Step 2 of Preparation 11,using 6-butyl-2-(methylthio)pyrimidin-4(3H)-one prepared in Step 1 ofPreparation 11 and 2-nitrobenzene-1,4-diamine.

¹H-NMR (400 MHz, CD₃OD) δ 8.45 (s 1H), 7.47 (d, 1H), 6.96 (d, 1H), 5.73(s, 1H), 4.61 (brs, 2H), 2.45 (d, 2H), 1.71-1.67 (m, 2H), 1.42-1.37 (m,2H), 0.96 (t, 3H); (Yield: 85%)

<Step 2> N¹-(4-butyl-6-chloropyrimidin-2-yl)-3-nitrobenzene-1,4-diamine

The titled compound in the form of pale yellow solid was prepared inaccordance with the same procedures as in Step 2 of Preparation 9, using2-(4-amino-3-nitrophenylamino)-6-butylpyrimidin-4(3H)-one prepared inStep 1 and phosphorus oxychloride.

¹H-NMR (400 MHz, CDCl₃) δ 8.65 (s, 1H), 7.77 (d, 1H), 7.48 (brs, 1H),7.20 (d, 1H), 6.80 (s, 1H), 2.72 (dd, 2H), 1.77-1.71 (m, 2H), 1.46-1.40(m, 2H), 0.98 (t, 3H); (Yield: 37%)

Preparation 17. (R)-3-hydroxypyrrolidine hydrochloride

Hydrogen chloride gas was added at 0° C. to a solution of(R)-1-(tert-butoxycarbonyl)-3-pyrrolidinol (3 g, 16.0 mmol) in ethylacetate (100 ml). The reaction mixture was stirred at room temperatureovernight and then filtered. The resulting white solid was dried invacuo to give 1.3 g of the titled compound.

¹H-NMR (400 MHz, CD₃OD) δ 4.55 (m, 1H), 3.41-3.36 (m, 2H), 3.22 (m, 2H),2.06-2.04 (m, 2H)

Preparation 18. (S)-3-methoxypyrrolidine <Step 1>(S)-3-methoxypyrrolidin-1-carboxylic acid tert-butyl ester

Sodium hydride (32 mg, 0.81 mmol, 60 wt %) was added at 0° C. to asolution of (S)-1-(tert-butoxycarbonyl)-3-pyrrolidinol (100 mg, 0.53mmol) in N,N-dimethylformamide (2 ml). The reaction mixture was stirredfor 30 minutes and iodomethane (99.7 μl, 1.60 mmol) was added thereto.The reaction mixture was stirred at room temperature overnight and thenwater was added thereto. The reaction mixture was concentrated underreduced pressure. The resulting residue was dissolved indichloromethane. The resulting solution was washed with water, dried onanhydrous sodium sulfate, and then concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=5/2) to give 50 mg of the titled compound ascolorless oil.

¹H-NMR (400 MHz, CDCl₃) δ 4.55 (m, 1H), 3.41-3.36 (m, 2H), 3.22 (m, 2H),2.06-2.04 (m, 2H)

<Step 2> (S)-3-methoxypyrrolidine

Trifluoroacetic acid (0.5 ml) was added to a solution of(S)-3-methoxypyrrolidin-1-carboxylic acid tert-butyl ester (50 mg, 0.25mmol) prepared in Step 1 in dichloromethane (5 ml). The reaction mixturewas stirred at room temperature for 1 hour and then concentrated underreduced pressure. The resulting residue was dissolved in dichloromethaneand then basified with an aqueous saturated solution of sodiumbicarbonate. The resulting organic layer was dried on anhydrous sodiumsulfate and then concentrated under reduced pressure to give 7.5 mg ofthe titled compound as pale yellow oil. The product was used in thesubsequent step without further purification.

Preparation 19. 2,5-diaminobenzonitrile

A mixture of 5-nitroanthranilonitrile (200 mg, 1.23 mmol) andpalladium/charcoal (10 mg, 10 wt %) in methanol (3 ml) was stirred atroom temperature under hydrogen atmosphere overnight and then filteredthrough a celite pad. The resulting filtrate was concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (n-hexane/ethyl acetate=1/2) to give 160.3 mg ofthe titled compound as a pale yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.79 (d, 1H), 6.72 (s, 1H), 6.61 (d, 1H), 4.01(brs, NH), 3.45 (brs, NH)

Preparation 20.(S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanol

The titled compound in the form of colorless oil was prepared inaccordance with the same procedures as Step 2 of Preparation 2, using2,4-dichloro-6-propylpyrimidine prepared in Step 1 of Preparation 2 and(S)-(+)-2-pyrrolidinemethanol.

¹H-NMR (400 MHz, CDCl₃) δ 6.08 (s, 1H), 4.79 (br, 1H), 4.34 (br, 1H),3.74 (m, 1H), 3.65 (m, 1H), 3.47-3.39 (m, 2H), 2.54 (t, 2H), 2.11-2.01(m, 3H), 1.99 (br, 1H), 1.76 (m, 2H), 1.62 (s, 1H), 0.92 (t, 3H);(Yield: 47%)

Preparation 21. (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate

2,4-Dichloro-6-propylpyrimidine (1.5 g, 7.85 mmol) prepared in Step 1 ofPreparation 2 was dissolved in ethanol (10 ml) and then(3S)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine (2.9 g, 15.7 mmol) wasadded thereto at 0° C. The reaction mixture was stirred at roomtemperature overnight and then concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1) to give 1.2 g of the titled compound as awhite solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.02 (s, 1H), 4.67 (br, 1H), 4.33 (br, 1H),3.84 (br, 2H), 3.24 (br, 2H), 2.54 (t, 2H), 2.26 (m, 1H), 1.93 (br, 1H),1.71 (m, 2H), 1.45 (s, 9H), 0.95 (t, 3H)

Preparation 22. 1H-benzo[d]imidazol-5-amine

5-nitrobenzimidazole (200 mg, 1.2 mmol) was dissolved in a mixed solventof methanol and tetrahydrofuran (1:1, 10 ml) and then palladium/charcoal(200 mg, 10 wt %) was added thereto. The reaction mixture was stirred atroom temperature under hydrogen atmosphere (30 bar) for 3 hours and thenfiltered through a celite pad. The resulting filtrate was concentratedunder reduced pressure to give 150 mg of the titled compound as a paleyellow solid. The product was used in the subsequent reaction withoutfurther purification.

Preparation 23. 2-methylbenzene-1,4-diamine

The titled compound (54 mg) in the form of pale yellow solid wasprepared in accordance with the same procedures as in Preparation 22,using 2-methyl-4-nitroaniline. The product was used in the subsequentreaction without further purification.

Preparation 24.(S)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl]acetamide <Step1>6-butylpyrimidin-2,4-diol

A mixture of 6-butyl-2-(methylthio)pyrimidin-4(3H)-one (2.1 g, 10.6mmol) prepared in Step 1 of Preparation 11, acetic acid (15 ml) andwater (7 ml) was refluxed under stirring for 2 days. The reactionmixture was cooled to room temperature and then concentrated underreduced pressure. The resulting residue was dried in vacuo to give 1.7 gof the titled compound as a pale yellow solid.

¹H-NMR (400 MHz, DMSO-d₆) δ 10.87 (brs, OH), 10.78 (brs, OH), 5.31 (s,1H), 2.27 (m, 2H), 1.50 (m, 2H), 1.27 (m, 2H), 0.88 (t, 3H)

<Step 2>4-butyl-2,6-dichloropyrimidine

A mixture of 6-butylpyrimidin-2,4-diol (1.7 g, 10.2 mmol) prepared inStep 1 and phosphorus oxychloride (5 ml) was refluxed under stirring for1 hour. The reaction mixture was cooled to room temperature, added toice water, and then basified to pH 8 with sodium bicarbonate. Theaqueous layer was extracted with ethyl acetate. The resulting organiclayer was dried on anhydrous magnesium sulfate and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (ethyl acetate/n-hexane=1/50) to give 1.435 gof the titled compound as brown oil.

¹H-NMR (400 MHz, CDCl₃) δ 7.16 (s, 1H), 2.75 (t, 2H), 1.71 (m, 2H), 1.40(m, 2H), 0.95 (t, 3H)

<Step 3>(S)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl]acetamide

The titled compound in the form of colorless oil was prepared inaccordance with the same procedures as in Preparation 13, using4-butyl-2,6-dichloropyrimidine prepared in Step 2 and(3S)-(−)-3-acetamidopyrrolidine.

¹H-NMR (400 MHz, CDCl₃) δ 7.25 (brs, NH), 6.02 (s, 1H), 4.54 (m, 1H),3.64-3.41 (m, 4H), 2.54 (t, 2H), 2.24 (m, 1H), 2.04-2.01 (m, 1H+3H),1.63 (m, 2H), 1.36 (m, 2H), 0.93 (t, 3H); (Yield: 56%)

Preparation 25. (S)-tert-butyl1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate

Diisopropylethylamine (4.46 ml, 25.6 mmol) was added to a solution of4-butyl-2,6-dichloropyrimidine (2.5 g, 12.1 mmol) prepared in Step 2 ofPreparation 24 and (3S)-(−)-3-(methylamino)pyrrolidine (1.43 ml, 13.4mmol) in chloroform (50 ml). The reaction mixture was stirred at 50° C.for 3 hours and then di-tert-butyldicarbonate (2.66 g, 12.2 mmol) wasadded thereto. The reaction mixture was stirred at room temperatureovernight, washed with water, dried on anhydrous magnesium sulfate, andthen concentrated under reduced pressure. The resulting residue waspurified with silica gel column chromatography (ethylacetate/n-hexane=1/5) to give 3.29 g of the titled compound as colorlessoil.

¹H-NMR (400 MHz, CDCl₃) δ 6.02 (s, 1H), 4.81 (m, 1H), 3.50 (m, 4H), 2.80(s, 3H), 2.56 (t, 2H), 2.17 (m, 1H), 1.67 (m, 2H), 1.48 (s, 9H+1H), 1.36(m, 2H), 0.93 (t, 3H)

Preparation 26. (S)-tert-butyl1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(ethyl)carbamate

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as in Preparation 25, using4-butyl-2,6-dichloropyrimidine prepared in Step 2 of Preparation 24 and(3S)-(−)-3-(ethylamino)pyrrolidine.

¹H-NMR (400 MHz, CDCl₃) δ 6.00 (s, 1H), 4.64 (m, 1H), 3.91-3.14 (m, 6H),2.55 (t, 2H), 2.18 (m, 1H), 1.65 (m, 2H), 1.47 (s, 9H+1H), 1.37 (m, 2H),1.15 (t, 3H), 0.92 (t, 3H); (Yield: 74%)

Preparation 27.(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]-2-hydroxyacetamide<Step 1> (S)-1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-amine

Diisopropylethylamine (1.09 ml, 6.28 mmol) was added to a solution of2,4-dichloro-6-propylpyrimidine (1 g, 5.23 mmol) prepared in Step 1 ofPreparation 2 and (S)-(−)-3-aminopyrrolidine (0.55 ml, 6.28 mmol) inethanol (30 ml), which was then stirred at room temperature overnight.Dichloromethane was added to the reaction mixture, which was then washedwith water. The organic layer was dried on anhydrous magnesium sulfate,and then concentrated under reduced pressure. The resulting residue wasused in the subsequent reaction without further purification.

<Step 2>(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]-2-hydroxyacetamide

A mixture of (S)-1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-amine(1.25 g, 5.23 mmol) prepared in Step 1, glycolic acid (0.44 g, 5.79mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.1g, 5.79 mmol), 1-hydroxybenzotriazole hydrate (0.78 g, 5.79 mmol),diisopropylethylamine (1.8 ml, 10.3 mmol), and dichloromethane (30 ml)was stirred at room temperature for 3 days. The reaction mixture wasdiluted with dichloromethane, washed with water and an aqueous saturatedsolution of sodium bicarbonate, dried on anhydrous sodium sulfate, andthen concentrated under reduced pressure. The resulting residue waspurified with silica gel column chromatography(dichloromethane/methanol=20/1) to give 680 mg of the titled compound asa white solid.

¹H-NMR (400 MHz, CDCl₃) δ 6.65 (s, NH), 6.03 (s, 1H), 4.65 (m, 1H), 4.14(s, 2H), 3.80-3.41 (m, 4H), 2.54 (t, 2H), 2.39 (m, 1H), 2.10 (m, 1H),1.72 (m, 2H), 0.96 (t, 3H)

Preparation 28. (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate

2,4-Dichloro-6-propylpyrimidine (2 g, 10.5 mmol) prepared in Step 1 ofPreparation 2 and diisopropylethylamine (4.6 ml, 26.3 mmol) weredissolved in chloroform (100 ml) and (3S)-(−)-3-(methylamino)pyrrolidine(1.1 g, 10.5 mmol) was added thereto at room temperature. The reactionmixture was then stirred at 50° C. for 1 hour and then cooled to roomtemperature. Di-tert-butyl dicarbonate (2.5 g, 11.6 mmol) was added tothe reaction mixture, which was then was stirred at 50° C. for 1 hour.Water was added to the reaction mixture, which was then extracted withethyl acetate. The organic layer was dried on anhydrous sodium sulfate,filtered, and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(n-hexane/ethyl acetate=3/1) to give 2.1 g of the titled compound aspale yellow oil.

¹H-NMR (400 MHz, CDCl₃) δ 6.02 (s, 1H), 4.85 (brs, 1H), 4.00-3.10 (m,4H), 2.80 (s, 3H), 2.54 (t, 2H), 2.30-2.00 (m, 2H), 1.80-1.60 (m, 2H),1.48 (s, 9H), 0.96 (t, 3H)

Preparation 29. (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(ethyl)carbamate

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Preparation 28, using2,4-dichloro-6-propylpyrimidine prepared in Step 1 of Preparation 2 and(3S)-(−)-3-(ethylamino)pyrrolidine.

¹H-NMR (400 MHz, CDCl₃) δ 6.01 (s, 1H), 4.63 (brs, 1H), 3.91 (brs, 1H),3.70-3.10 (m, 5H), 2.53 (t, 2H), 2.30-2.05 (m, 2H), 1.72 (q, 2H), 1.48(s, 9H), 1.15 (t, 3H), 0.95 (t, 3H); (Yield: 65%)

Preparation 30.4-chloro-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine<Step1>2-{[4-fluoro-3-(trifluoromethyl)phenyl]amino}-6-propylpyrimidin-4(3H)-one

A mixture of 2-(methylthio)-6-propylpyrimidin-4(3H)-one (1.8 g, 9.8mmol) prepared in Step 1 of Preparation 1 and5-amino-2-fluorobenzotrifluoride (2 g, 11.2 mmol) was stirred at 160° C.overnight. The reaction mixture was cooled to 80° C. and then ethylacetate (20 ml) was added thereto. The reaction mixture was refluxedunder stirring for 1 hour and then filtered to give 2.2 g of the titledcompound as a white solid.

¹H-NMR (400 MHz, CD₃OD) δ 8.20 (s, 1H), 7.80-7.70 (m, 1H), 7.29 (t, 1H),5.81 (s, 1H), 2.46 (t, 2H), 1.73 (q, 2H), 0.98 (t, 3H)

<Step2>4-chloro-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine

A mixture of2-{[4-fluoro-3-(trifluoromethyl)phenyl]amino}-6-propylpyrimidin-4(3H)-one(2.2 g, 7.0 mmol) prepared in Step 1 and phosphorus oxychloride (10 ml)was stirred at 110 overnight. The reaction mixture was cooled to roomtemperature, added to ice water, and then basified to pH 9 with sodiumhydroxide. The aqueous layer was extracted with ethyl acetate. Theresulting organic layer was dried on anhydrous sodium sulfate and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=4/1) togive 2 g of the titled compound as a yellow solid.

¹H-NMR (400 MHz, CDCl₃) δ 8.27 (brs, 1H), 8.09 (s, 1H), 7.71 (d, 1H),7.16 (t, 1H), 6.69 (s, 1H), 2.64 (t, 2H), 1.76 (q, 2H), 0.98 (t, 3H)

The synthetic method for the compounds (including the salt thereof) ofthe present invention is described in the following working examples.And also, the compounds of the following working examples and the NMRspectrum data are shown in the subsequent Tables 1-1 to 1-51.

Example 1

A solution of 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine (20mg, 0.08 mmol) prepared in Preparation 1 and pyrrolidine (25 mg, 0.35mmol) in isopropanol (1 ml) was stirred at 100 overnight. The reactionmixture was cooled to room temperature and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (n-hexane/ethyl acetate=4/1) to give 20 mg of theproduct as a pale yellow solid.

Examples 2 to 24

The products of Examples 2 to 24 were prepared in accordance with thesame procedures as in Example 1, using4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine prepared inPreparation 1; and (S)-2-pyrrolidinemethanol, 3-pyrrolidinol,D-prolinol, DL-prolinol, 2-methylpyrrolidine,(S)-2-(methoxymethyl)pyrrolidine, (R)-2-(methoxymethyl)pyrrolidine,(S)-pyrrolidin-2-carboxamide, 3-acetamidopyrrolidine,(3R)-(+)-3-acetamidopyrrolidine,2,2,2-trifluoro-N-(pyrrolidin-3-yl)acetamide, 3-(ethylamino)pyrrolidine,3-(dimethylamino)pyrrolidine,(S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine,(S)-(+)-2-(anilinomethyl)pyrrolidine, (3S)-(−)-3-acetamidopyrrolidine,(3S)(−)-3-(ethylamino)pyrrolidine,(3S)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine, 3-aminopyrrolidine,3-(diethylamino)pyrrolidine, (3S)-(−)-3-(methylamino)pyrrolidine,3-(N-acetyl-N-methylamino)pyrrolidine, or (S)-3-pyrrolidinol.

Example 25

A solution of 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine (20mg, 0.08 mmol) prepared in Preparation 1 and 3-(ethylamino)pyrrolidine(0.25 g, 2.25 mmol) in isopropanol (3 ml) was stirred at 100 overnight.The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=1/2) andthen dissolved in ethyl acetate (2 ml). Hydrogen chloride gas was addedto the resulting solution and then filtered to give 0.33 g of theproduct as a white solid.

Example 26

A mixture of(S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine(0.4 g, 1.4 mmol) prepared in Preparation 2 and 6-aminoindole (0.28 g,2.1 mmol) in n-butanol (1 ml) was refluxed under stirring overnight. Thereaction mixture was cooled to room temperature and then filtered togive 0.25 g of the product as a pale yellow solid.

Example 27

A mixture of(S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidine (20mg, 0.07 mmol) prepared in Preparation 2 and 5-aminoindole (30 mg, 0.23mmol) in n-butanol (1 ml) was refluxed under stirring overnight. Thereaction mixture was cooled to room temperature and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (n-hexane/ethyl acetate=1/1) to give 5.2 mg ofthe product as a pale yellow solid.

Examples 28 to 46

The products of Examples 28 to 46 were prepared in accordance with thesame procedures as in Example 27, using(S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidineprepared in Preparation 2; and 4-methoxyaniline, 3-methoxyaniline,3-chloroaniline, 4-fluoro-3-nitroaniline, 3-nitroaniline,4-chloro-3-nitroaniline, 3-aminobenzonitrile, 3-(methylthio)aniline,3-(trifluoromethyl)aniline, 7-amino-4-methyl-2H-chromen-2-one,5-chloro-2-methylaniline, 4-amino-2-chlorotoluene,4-methyl-3-nitroaniline, 4-fluoro-3-(trifluoromethyl)aniline,2-(trifluoromethyl)benzene-1,4-diamine, 5-amino-2-fluorobenzonitrile,5-amino-2-methylbenzonitrile, 2,5-diaminobenzonitrile prepared inPreparation 19, or 2-nitro-1,4-phenylenediamine.

Example 47

(S)-tert-Butyl1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate(10 mg, 0.02 mmol) prepared in Example 19 was dissolved in ethyl acetate(1 ml) and then hydrogen chloride gas was added thereto. The reactionmixture was stirred at room temperature for 1 hour and then filtered togive 7 mg of the product as a white solid.

Examples 48 to 58

The products of Examples 48 to 58 were prepared in accordance with thesame procedures as in Example 1, using3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile prepared inPreparation 3; and (3S)-(−)-3-(tert-butoxycarbonylamino)pyrrolidine,3-(diethylamino)pyrrolidine, (3S)-(−)-3-(methylamino)pyrrolidine,3-(N-acetyl-N-methylamino)pyrrolidine, (S)-3-pyrrolidinol,(R)-(−)-2-methylpyrrolidine, (3S)-(−)-3-acetamidopyrrolidine,(3S)-(−)-3-(ethylamino)pyrrolidine,(3S)-(−)-3-(N-tert-butoxycarbonylaminomethyl)pyrrolidine,(R)-3-hydroxypyrrolidine hydrochloride prepared in Preparation 17, or(S)-3-methoxypyrrolidine prepared in Preparation 18.

Example 59

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 25, using3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile prepared inPreparation 3 and 3-(methylamino)pyrrolidine.

Example 60

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 47, using (S)-tert-Butyl1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamateprepared in Example 48.

Example 61

A mixture of(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride (20 mg, 0.05 mmol) prepared in Example 60, butyric acid(7 mg, 0.08 mol),(benzotriazole-1-yloxy)-tris-(dimethylamino)phosphoniumhexafluorophosphate (31.8 mg, 0.06 mmol), diisopropylethylamine (25.9mg, 0.2 mmol), and N,N-dimethylformamide (1 ml) was stirred at roomtemperature overnight. Water was added to the reaction mixture, whichwas then extracted with ethyl acetate. The organic layer was washed withbrine, dried on anhydrous magnesium sulfate, filtered, and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=1/1) togive 10.5 mg of the product as a pale yellow solid.

Examples 62 to 82

The products of Examples 62 to 82 were prepared in accordance with thesame procedures as in Example 61, using(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride prepared in Example 60; and cyclopentanecarboxylic acid,1-piperidinepropionic acid, benzoic acid, 4-fluorobenzoic acid,phenylacetic acid, 4-fluorophenylacetic acid, 3-phenoxypropionic acid,3-isobutoxypropanoic acid, 2-(4-benzylpiperazin-1-yl)acetic acid,2-(piperidin-1-yl)acetic acid, 3-benzoylpropionic acid,4-aminophenylacetic acid, cyclopentylacetic acid, methoxyacetic acid,2-pyridylacetic acid, 3-pyridylacetic acid, 4-pyridylacetic acid,trans-styrylacetic acid, 2-thiopheneacetic acid, isobutanoic acid or3,3,3-trifluoropropanoic acid.

Example 83

A mixture of 3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile (20mg, 0.07 mmol) prepared in Preparation 3, 2-pyrrolidone (9.4 mg, 0.11mmol), palladium acetate (0.16 mg, 0.7 μmol),4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.3 mg, 2.1 μmol),cesium carbonate (71.4 mg, 0.22 mmol), and 1,4-dioxane (1 ml) wasstirred at 110° C. overnight and then concentrated under reducedpressure. The resulting residue was purified with silica gel columnchromatography (n-hexane/ethyl acetate=4/1) to give 5 mg of the productas a pale yellow solid.

Example 84

(S)-3-[4-(3-Aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride (20 mg, 0.05 mmol) prepared in Example 60 andhexylaldehyde (5 mg, 0.05 mmol) in methanol (1 ml) was stirred at roomtemperature for 30 minutes and sodium cyanoborohydride (9.4 mg, 0.15mmol) was added thereto. The reaction mixture was stirred at roomtemperature for 3 hours and then an aqueous saturated solution of sodiumbicarbonate was added thereto to terminate the reaction. The reactionmixture was extracted with ethyl acetate. The organic layer was dried onanhydrous sodium sulfate, filtered, and then concentrated. The resultingresidue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1) to give 10 mg of the product as a paleyellow solid.

Examples 85 to 117

The products of Examples 85 to 117 were prepared in accordance with thesame procedures as in Example 84, using(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride prepared in Example 60; and propionaldehyde,cyclohexanecarboxaldehyde, benzaldehyde, phenylacetaldehyde,3-phenylpropionaldehyde, 3-fluorobenzaldehyde, 4-hydroxybenzaldehyde,4-ethylbenzaldehyde, 3-methylbutanal, pentanal, 2-methylbutanal,2-methylpropanal, 4-methoxybenzaldehyde, 4-fluorobenzaldehyde,cyclopropanecarboxaldehyde, cyclopropanecarboxaldehyde (2 eq.),2-pyridinecarboxaldehyde, 3-pyridinecarboxaldehyde,4-pyridinecarboxaldehyde, 2-ethylbutanal, pivaldehyde,2-fluorobenzaldehyde, 3-(trifluoromethyl)benzaldehyde,4-(trifluoromethyl)benzaldehyde, 4-acetoxybenzaldehyde,4-(dimethylamino)benzaldehyde, pyrrole-2-carboxaldehyde,thiophene-2-carboxaldehyde, thiophene-3-carboxaldehyde, butanal (2 eq.),3-(methylthio)propionaldehyde (2 eq.), butanal, or3-(methylthio)propionaldehyde.

Example 118

(S)-3-{4-Propyl-6-[3-(propylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile(20 mg, 0.05 mmol) prepared in Example 85 was dissolved in ethyl acetate(1 ml) and hydrochloric acid was added thereto. The reaction mixture wasstirred at room temperature for 1 hour and then filtered to give 15.5 mgof the product as a white solid.

Examples 119

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)-3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrileprepared in Example 99.

Examples 120

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)-3-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrileprepared in Example 50.

Example 121

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 1, usingN-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine prepared inPreparation 4 and (3S)-(−)-3-(methylamino)pyrrolidine.

Example 122

A mixture of(S)-1-(2-chloro-6-propylpyrimidin-4-yl)-N-methylpyrrolidin-3-amine (0.4g, 1.57 mmol) prepared in Preparation 5 and 6-aminoindole (0.21 g, 1.57mmol) in n-butanol (2 ml) was refluxed under stirring overnight. Thereaction mixture was cooled to room temperature and then filtered. Theresulting solid was dried to give 0.2 g of the product as a pale yellowsolid.

Example 123

A mixture of(S)-1-(2-chloro-6-propylpyrimidin-4-yl)-N-methylpyrrolidin-3-amine (1 g,3.93 mmol) in prepared in Preparation 5 and2-(trifluoromethyl)-1,4-phenylenediamine (0.7 g, 3.93 mmol) in n-butanol(10 ml) was refluxed under stirring overnight. The reaction mixture wascooled to room temperature and then concentrated under reduced pressure.The resulting residue was diluted with dichloromethane, washed with anaqueous saturated solution of sodium bicarbonate, dried on anhydroussodium sulfate, and then concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(dichloromethane/methanol=10/1) and then dissolved in ethyl acetate (10ml). Hydrogen chloride gas was added to the solution and then filteredto give 0.4 g of the product as a white solid.

Example 124

A mixture of(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride (20 mg, 0.05 mmol) prepared in Example 60, triethylamine(20 mg, 0.2 mmol), isopropylsulfonyl chloride (8 mg, 0.05 mmol), andN,N-dimethylformamide (1 ml) was stirred at room temperature for 4hours. Water was added to the reaction mixture, which was then extractedwith ethyl acetate. The organic layer was washed with brine, dried onanhydrous magnesium sulfate, filtered, and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (n-hexane/ethyl acetate=1/1) to give 9.5 mg of theproduct as a pale yellow solid.

Examples 125 and 126

The products of Examples 125 and 126 were prepared in accordance withthe same procedures as in Example 124, using(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride prepared in Example 60; and methanesulfonyl chloride or4-fluorobenzenesulfonyl chloride.

Example 127

A solution of(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride (30 mg, 0.08 mmol) prepared in Example 60 and methylethyl ketone (18 mg, 0.25 mmol) in methanol (0.8 ml) was stirred at roomtemperature for 30 minutes. Sodium triacetoxyborohydride (71.2 mg, 0.34mmol) and a catalytic amount of acetic acid were added thereto. Thereaction mixture was stirred at room temperature overnight and then anaqueous saturated solution of sodium bicarbonate was added thereto toterminate the reaction. The reaction mixture was extracted withdichloromethane. The organic layer was dried on anhydrous sodiumsulfate, filtered, and then concentrated. The resulting residue waspurified with silica gel column chromatography(dichloromethane/methanol=50/1) to give 32 mg of the product as a whitesolid.

Examples 128 to 145

The products of Examples 128 to 145 were prepared in accordance with thesame procedures as in Example 127, using(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride prepared in Example 60; and 3-pentanone,2,6-dimethyl-4-heptanone, 4,4-dimethyl-2-pentanone,3-hydroxy-3-methyl-2-butanone, 4-heptanone, 2-hexanone,5-methyl-2-hexanone, cyclohexanone, tert-butyl 2-oxoethylcarbamate,1-benzyl-4-piperidinone, acetone, 1-benzoyl-4-piperidone,1-acetyl-4-piperidone, cydooctanone, cydobutanone, cyclopentanone,tert-butyl 3-oxoazetidine-1-carboxylate, or 2-benzyloxyacetaldehyde.

Example 146

A mixture of(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride (18 mg, 0.05 mmol) prepared in Example 60, propionicacid (4.6 μl, 0.06 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimidehydrochloride (11.8 mg, 0.06 mmol), 1-hydroxybenzotriazole hydrate (8.3mg, 0.06 mmol), diisopropylethylamine (19.4 μl, 0.11 mmol), anddichloromethane (1 ml) was stirred at room temperature overnight. Thereaction mixture was diluted with dichloromethane, washed with water andan aqueous saturated solution of sodium bicarbonate, dried on anhydroussodium sulfate, and then concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(dichloromethane/methanol=70/1) to give 13.4 mg of the product as awhite solid.

Examples 147 to 167

The products of Examples 147 to 167 were prepared in accordance with thesame procedures as in Example 146, using(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride prepared in Example 60; and pivalic acid,2,2-dimethylbutyric acid, tiglic acid, hexanoic acid, 3-phenylpropionicacid, indole 3-acetic acid, 2-hydroxyisobutyric acid,3-(4-methoxyphenyl)propionic acid, 3-(4-hydroxyphenyl)propionic acid,levulinic acid, glycolic acid, benzyloxyacetic acid, phenoxyacetic acid,N,N-dimethylglycine hydrochloride, 3-(dimethylamino)propionic acidhydrochloride, 4-(dimethylamino)butyric acid hydrochloride, ethoxyaceticacid, 2-(2-methoxyethoxy)acetic acid, benzyloxycarbonylaminoacetic acid,N-(tert)-butoxycarbonyl-L-γ-aminobutyric acid, orpiperidine-1,4-dicarboxylic acid mono tert-butyl ester.

Example 168

A solution of(R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine (20 mg,0.083 mmol) prepared in Preparation 15 and 5-amino-2-methylbenzonitrile(12.6 mg, 0.091 mmol) in n-butanol (0.5 ml) was reacted in a microwavereactor (450 W) for 40 minutes. The reaction mixture was cooled to roomtemperature and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(dichloromethane/methanol=50/1) and then dissolved in ethyl acetate (1ml). Hydrogen chloride gas was added to the solution, which was thenstirred at room temperature for 1 hour. The reaction mixture wasfiltered to give 9 mg of the product as a white solid.

Example 169

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 168, using(R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine prepared inPreparation 15 and 2,5-diaminobenzonitrile prepared in Preparation 19.

Examples 170 and 171

The products of Examples 170 and 171 were prepared in accordance withthe same procedures as in Example 1, using5-(4-chloro-6-pro-6-proylpyrimidin-2-ylamino)-2-methylbenzonitrileprepared in Preparation 6; and (3S)-(−)-3-(methylamino)pyrrolidine or(3S)-(−)-3-(ethylamino)pyrrolidine.

Example 172

A mixture of5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile (20 mg,0.07 mmol) prepared in Preparation 6 and(3S)-(−)-3-(ethylamino)pyrrolidine (8 mg, 0.07 mmol) in isopropanol (1ml) was refluxed under stirring overnight. The reaction mixture wascooled to room temperature and then filtered. The resulting pale yellowsolid was dried to give to 12 mg of the product.

Example 173

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 172, using5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile preparedin Preparation 6 and 3-(ethylamino)pyrrolidine.

Example 174

A solution of5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile (200 mg,0.7 mmol) prepared in Preparation 6 and(3S)-(−)-3-(methylamino)pyrrolidine (69.9 mg, 0.7 mmol) in isopropanol(1.4 ml) was reacted in a microwave reactor (450 W) for 30 minutes. Thereaction mixture was cooled to room temperature and then filtered togive 209 mg of the product as a pale gray solid.

Examples 175 and 176

The products of Examples 175 and 176 were prepared in accordance withthe same procedures as in Example 1, usingN¹-(4-chloro-6-propylpyrimidin-2-yl)-3-nitrobenzene-1,4-diamine preparedin Preparation 7; and (3S)-(−)-3-(methylamino)pyrrolidine or(3S)-(−)-3-(ethylamino)pyrrolidine.

Example 177

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 172, usingN¹-(4-chloro-6-propylpyrimidin-2-yl)-3-nitrobenzene-1,4-diamine preparedin Preparation 7 and (3S)-(−)-3-(ethylamino)pyrrolidine.

Example 178

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 172, using3-(4-chloro-6-propylpyrimidin-2-yl)benzonitrile prepared in Preparation3 and (3S)-(−)-3-(methylamino)pyrrolidine.

Example 179

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 47, using (S)-tert-butyl{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methylcarbamateprepared in Example 56.

Examples 180 and 181

The products of Examples 180 and 181 were prepared in accordance withthe same procedures as in Example 172, using5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile preparedin Preparation 8; and (3S)-(−)-3-(methylamino)pyrrolidine or(3S)-(−)-3-(ethylamino)pyrrolidine.

Example 182

A solution of5-(4-chloro-6-propylpyrimidin-2-ylamino)-2-fluorobenzonitrile (0.2 g,0.67 mmol) prepared in Preparation 8 and3-(tert-butoxycarbonylamino)pyrrolidine (0.2 g, 1.0 mmol) in isopropanol(3 ml) was stirred at 100 overnight. The reaction mixture was cooled toroom temperature and then concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1) and then dissolved in ethyl acetate (1 ml).Hydrogen chloride gas was added to the solution, which was then stirredat room temperature for 1 hour. The reaction mixture was filtered togive 0.1 g of the product as a white solid.

Example 183

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 1, using4-chloro-N-(4-fluorophenyl)-6-methylpyrimidin-2-amine prepared inPreparation 10 and pyrrolidine.

Example 184 <Step1>(2S,4R)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]-4-hydroxypyrrolidin-2-carboxylicacid

A solution of 4-chloro-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine (50mg, 0.19 mmol) prepared in Preparation 1, trans-4-hydroxy-L-proline(27.3 mg, 0.21 mmol), and diisopropylethylamine (49 μl, 0.38 mmol) inisopropanol (1.0 ml) was reacted in a microwave reactor (500 W) for 30minutes. The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (dichloromethane/methanol=30/1) togive 30 mg of the titled compound.

<Step2>(2S,4R)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]-4-hydroxypyrrolidin-2-carboxylicacid methyl ester

A solution of(2S,4R)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]-4-hydroxypyrrolidin-2-carboxylicacid (30 mg, 0.08 mmol) prepared in Step 1 and a catalytic amount ofsulfuric acid in methanol (3 ml) was refluxed under stirring overnight.The reaction mixture was neutralized with an aqueous saturated solutionof sodium bicarbonate and then extracted with dichloromethane. Theorganic layer was dried on anhydrous sodium sulfate, filtered, and thenconcentrated to give 30 mg of the titled compound. The resulting productwas used in the subsequent reaction without further purification.

<Step3>(3R,5S)-1-[2-(4-fluorophenyl)-6-propylpyrimidin-4-yl]-5-(hydroxymethyl)pyrrolidin-3-ol

A solution of(2S,4R)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]-4-hydroxypyrrolidin-2-carboxylicacid methyl ester (20 mg, 0.05 mmol) prepared in Step 2 and sodiumborohydride (12.1 mg, 0.32 mmol) in ethanol (1 ml) was stirred for 3hours and then an aqueous saturated solution of ammonium chloride wasadded thereto to terminate the reaction. The reaction mixture wasextracted with dichloromethane. The organic layer was dried on anhydroussodium sulfate, filtered, and then concentrated. The resulting residuewas purified with silica gel column chromatography(dichloromethane/methanol=30/1) to give 14 mg of the titled compound asa white solid.

Example 185

A mixture of N-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine (13mg, 0.05 mmol) prepared in Preparation 4, (S)-pyrrolidin-2-ylmethanol(9.1 mg, 0.09 mmol), diisopropylethylamine (17.6 mg, 14 mol) inisopropanol (0.5 ml) was reacted in a microwave reactor (300 W) for 2hours. The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (n-hexane/ethyl acetate=2/1) togive 17.1 mg of the product as a yellow liquid.

Examples 186 to 192

The products of Examples 186 to 192 were prepared in accordance with thesame procedures as in Example 185, usingN-(4-chloro-6-propylpyrimidin-2-yl)-1H-indol-6-amine prepared inPreparation 4; and (R)-pyrrolidin-2-ylmethanol, pyrrolidin-2-ylmethanol,(R)-2-(methoxymethyl)pyrrolidine, (S)-2-(methoxymethyl)pyrrolidine,2-methylpyrrolidine, (S)-methylpyrrolidine-2-carboxylate, orN-(pyrrolidin-3-yl)acetamide.

Example 193

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 26, using(S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanolprepared in Preparation 20 and 6-aminoindole.

Examples 194 to 215

The products of Examples 194 to 215 were prepared in accordance with thesame procedures as in Example 27, using(S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanolprepared in Preparation 20; and 3-aminobenzonitrile,3-(methylthio)aniline, 4-chloro-3-nitroaniline, 5-aminoindole,1H-benzo[d]imidazol-5-amine prepared in Preparation 22,5-amino-2-(trifluoromethyl)benzimidazole, 4-methoxyaniline,3-chloroaniline, 3-methoxyaniline, 3-(trifluoromethyl)aniline,5-chloro-2-methylaniline, 5-methoxy-2-methylaniline,4-amino-2-chlorotoluene, 3-nitroaniline, 4-fluoro-3-nitroaniline,6-aminoquinoline, 4-methyl-3-nitroaniline,2-(trifluoromethyl)benzene-1,4-diamine, 3-nitro-1,4-phenylenediamine,5-amino-2-methylbenzonitrile, 5-amino-2-fluorobenzonitrile, or2,5-diaminobenzonitrile prepared in Preparation 19.

Example 216

3-Aminoquinoline (22 mg, 0.15 mmol) was added to a mixture of(S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanol (30 mg,0.12 mmol) prepared in Preparation 20, palladium acetate (0.5 mg, 2 mol%), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (2.1 mg, 3 mol %),cesium carbonate (78 mg, 0.24 mmol), and anhydrous 1,4-dioxane (1 ml).The reaction mixture was stirred in a microwave reactor (600 W) for 1hour. The reaction mixture was cooled to room temperature, suspended indichloromethane, and then filtered through a celite pad. The resultingfiltrate was concentrated under reduced pressure. The resulting residuewas purified with silica gel column chromatography (n-hexane/ethylacetate=1/1) to give 29.8 mg of the product as a pale yellow solid.

Example 217 <Step 1>(S)-1-(6-{4-[2-(hydroxylmethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}indolin-1-yl)ethanone

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as in Example 27, using(S)-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-2-yl]methanolprepared in Preparation 20 and 1-acetyl-6-aminoindoline. The product wasused in the subsequent reaction without further purification.

<Step 2>(S)-2-{1-[2-(indolin-6-ylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol

A mixture of(S)-1-(6-{4-[2-(hydroxylmethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}indolin-1-yl)ethanone(45.7 mg, 0.12 mmol) prepared in Step 1 and 3N hydrochloric acidsolution (1.5 ml) was refluxed under stirring for 2 hours. The reactionmixture was cooled to room temperature, basified to pH 8-9 with a 2Nsodium hydroxide solution, and then extracted with dichloromethane. Theresulting organic layer was dried on anhydrous sodium sulfate, and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (dichloromethane/methanol=40/1) togive 19.2 mg of the titled compound as colorless oil.

Example 218

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)-3-{4-[3-(cyclohexylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrileprepared in Example 135.

Example 219

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)-3-{4-[3-(isopropylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrileprepared in Example 138.

Example 220

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 47, using (S)-tert-butyl2-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}ethylcarbamateprepared in Example 136.

Example 221

A solution of(S)-3-{4-[3-(1-benzylpiperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile(110 mg, 0.22 mmol) prepared in Example 137 and palladium/charcoal (11mg, 10 wt %) in methanol (2.2 ml) was stirred at room temperature underhydrogen atmosphere for 5 hours and then filtered through a celite pad.The resulting filtrate was concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(dichloromethane/methanol=10/1) to give 28 mg of the product as a whitesolid.

Example 222

A solution of(S)-3-{4-[3-(piperidin-4-ylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile(15 mg, 0.04 mmol) prepared in Example 221 and butyraldehyde (2.7 mg,0.04 mmol) in methanol (0.4 ml) was stirred at room temperature for 30minutes and then sodium triacetoxyborohydride (15.7 mg, 0.08 mmol) wasadded thereto. The reaction mixture was stirred at room temperature for1 hour and then an aqueous saturated solution of sodium bicarbonate wasadded thereto to terminate the reaction. The reaction mixture wasextracted with dichloromethane. The resulting organic layer was dried onanhydrous sodium sulfate, filtered, and then concentrated. The resultingresidue was purified with silica gel column chromatography(dichloromethane/methanol=50/1) to give 4.0 mg of the product as a whitesolid.

Example 223

A solution of 3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile (20mg, 0.07 mmol) prepared in Preparation 11 and(S)—N-(pyrrolidin-3-yl)acetamide (9.8 mg, 0.08 mmol) in isopropanol (0.3ml) was reacted in a microwave reactor (450 W) for 30 minutes. Thereaction mixture was cooled to room temperature and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (dichloromethane/methanol=50/1) to give 26.7mg of the product as a white solid.

Examples 224 to 227

The products of Examples 224 to 227 were prepared in accordance with thesame procedures as in Example 223, using3-(4-butyl-6-chloropyrimidin-2-ylamino)benzonitrile prepared inPreparation 11; and (S)-pyrrolidin-2-ylmethanol,(R)-2-methylpyrrolidine, (3S)-(−)-3-(methylamino)pyrrolidine, or(S)-tert-butyl pyrrolidin-3-ylcarbamate.

Examples 228 to 232

The products of Examples 228 to 232 were prepared in accordance with thesame procedures as in Example 223, using5-(4-butyl-6-chloropyrimidin-2-ylamino)-2-methylbenzonitrile prepared inPreparation 12; and (S)—N-(pyrrolidin-3-yl)acetamide,(S)-pyrrolidin-2-ylmethanol, (R)-2-methylpyrrolidine,(3S)-(−)-3-(methylamino)pyrrolidine, or (S)-tert-butylpyrrolidin-3-ylcarbamate.

Example 233

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 47, using (S)-tert-butyl1-[6-butyl-2-(3-cyanophenylamino)pyrimidin-4-yl]pyrrolidin-3-ylcarbamateprepared in Example 227.

Example 234

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 47, using (S)-tert-butyl1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl)pyrrolidin-3-ylcarbamateprepared in Example 232.

Examples 235 to 237

The products of Examples 235 to 237 were prepared in accordance with thesame procedures as in Example 127, using(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-butylpyrimidin-2-ylamino]benzonitriledihydrochloride prepared in Example 233; and acetone, acetaldehyde (2eq.), or cydopropanecarboxaldehyde.

Examples 238 to 240

The products of Examples 238 to 240 were prepared in accordance with thesame procedures as in Example 127, using(S)-5-[4-(3-aminopyrrolidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride prepared in Example 234; and acetone, acetaldehyde (2eq.), or cydopropanecarboxaldehyde.

Example 241

A solution of(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide (20mg, 0.07 mmol) prepared in Preparation 13 and 4-chloro-3-nitroaniline(13.5 mg, 0.08 mmol) in n-butanol (0.5 ml) was reacted in a microwavereactor (450 W) for 50 minutes. The reaction mixture was cooled to roomtemperature and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(dichloromethane/methanol=50/1) to give 26.1 mg of the product as a paleyellow solid.

Examples 242 to 259

The products of Examples 242 to 259 were prepared in accordance with thesame procedures as in Example 241, using(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamideprepared in Preparation 13; and 3-(methylthio)aniline, 6-aminoindole,3-(trifluoromethyl)aniline, 7-amino-4-methyl-2H-chromen-2-one,2-chloro-4-aminotoluene, 3-nitroaniline, 4-fluoro-3-nitroaniline,4-methyl-3-nitroaniline, benzyl 5-amino-2-methoxyphenylcarbamate,5-amino-2-fluorobenzonitrile, 5-amino-2-methylbenzonitrile,4-fluoro-3-(trifluoromethyl)aniline, 2-nitrobenzene-1,4-diamine,5-chloro-2-methylaniline, 3-aminobenzamide, 3-amino-N-methylbenzamide,3-aminobenzylamine, or 3-amino-4-chlorobenzamide.

Example 260

A solution of(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide (20mg, 0.08 mmol) prepared in Preparation 13 and 2,5-diaminobenzonitrile(9.5 mg, 0.07 mmol) prepared in Preparation 19 in n-butanol (0.5 ml) wasreacted in a microwave reactor (450 W) for 40 minutes. The reactionmixture was cooled to room temperature and then filtered to give 17.1 mgof the product as a yellow solid.

Examples 261 and 262

The products of Examples 261 and 262 were prepared in accordance withthe same procedures as in Example 260, using(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamideprepared in Preparation 13; and 2-(trifluoromethyl)-1,4-phenylenediamineor 3,5-diaminobenzonitrile.

Examples 263 to 273

The products of Examples 263 to 273 were prepared in accordance with thesame procedures as in Example 26, using(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamideprepared in Preparation 13; and 6-aminoindole, 5-chloro-2-methylaniline,4-fluoro-3-(trifluoromethyl)aniline, 4-fluoro-1,3-diaminobenzene,3-(trifluoromethyl)aniline, 5-(trifluoromethyl)-1,3-phenylenediamine,3-nitroaniline, 1,4-phenylenediamine, 5-amino-2-chlorophenol,4-aminosalicylic acid, or 5-aminosalicylic acid.

Examples 274 to 282

The products of Examples 274 to 282 were prepared in accordance with thesame procedures as in Example 27, using(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamideprepared in Preparation 13; and 5-amino-o-cresol,4-amino-2-chlorophenol, 4-amino-o-cresol, 4-amino-2-fluorophenol,3-hydroxy-4-methoxyaniline, 3-methoxy-4-methylaniline,4-methyl-3-(trifluoromethyl)aniline, 3,4-dimethylaniline, or3-fluoro-4-methylaniline.

Example 283

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 248.

Example 284

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 249.

Example 285

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 252.

Example 286

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 254.

Example 287

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 54.

Example 288

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 241.

Example 289

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 221, using (S)-benzyl5-[4-(3-acetamidopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methoxyphenylcarbamateprepared in Example 250.

Example 290

The product in the form of pale yellow oil was prepared in accordancewith the same procedures as in Example 221, using(S)—N-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 241.

Example 291

The product in the form of pale yellow oil was prepared in accordancewith the same procedures as in Example 221, using(S)—N-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 248.

Example 292

The product in the form of pale yellow oil was prepared in accordancewith the same procedures as in Example 221, using(S)—N-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 249.

Example 293

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 260, usingN-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide preparedin Preparation 14 and 2-nitrobenzene-1,4-diamine.

Examples 294 to 309

The products of Examples 294 to 309 were prepared in accordance with thesame procedures as in Example 27, usingN-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide preparedin Preparation 14; and 3-aminobenzonitrile, 3-nitroaniline,4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline, 3-methoxyaniline,5-methoxy-2-methylaniline, 4-methoxyaniline, 3-(trifluoromethyl)aniline,3-chloroaniline, 5-chloro-2-methylaniline, 2-chloro-4-aminotoluene,3-(methylthio)aniline, 5-aminoindole,5-amino-2-(trifluoromethyl)benzimidazole, 6-aminoquinoline, or7-amino-4-methyl-2H-chromen-2-one.

Example 310

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 216, usingN-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide preparedin Preparation 14 and 3-aminoquinoline.

Examples 311 and 312 The products of Examples 311 and 312 were preparedin accordance with the same procedures as in Example 26, usingN-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]acetamide preparedin Preparation 14 and 2,5-diaminobenzonitrile prepared in Preparation 19or 4-fluoro-1,3-phenylenediamine.

Examples 313 to 329

The products of Examples 313 to 329 were prepared in accordance with thesame procedures as in Example 241, using(R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine prepared inPreparation 15; and 4-chloro-3-nitroaniline, 3-(methylthio)aniline,6-aminoindole, 3-(trifluoromethyl)aniline,7-amino-4-methyl-2H-chromen-2-one, 2-chloro-4-aminotoluene,3-nitroaniline, 4-fluoro-3-nitroaniline, 4-methyl-3-nitroaniline,4-fluoro-3-(trifluoromethyl)aniline,2-(trifluoromethyl)-1,4-phenylenediamine, benzyl5-amino-2-methoxyphenylcarbamate, 5-amino-2-fluorobenzonitrile,5-amino-2-methylbenzonitrile, 2,5-diaminobenzonitrile prepared inPreparation 19, 2-nitrobenzene-1,4-diamine, or1-(6-aminoindolin-1-yl)ethanone.

Example 330

The product in the form of pale yellow oil was prepared in accordancewith the same procedures as in Example 216, using(R)-2-chloro-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidine prepared inPreparation 15 and 5-chloro-2-methylaniline.

Example 331

The product in the form of pale yellow oil was prepared in accordancewith the same procedures as in Example 221, using (R)-benzyl2-methoxy-5-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]phenylcarbamateprepared in Example 324.

Example 332

The product in the form of pale yellow oil was prepared in accordancewith the same procedures as in Example 221, using(R)—N-(4-chloro-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amineprepared in Example 313.

Example 333

The product in the form of pale yellow oil was prepared in accordancewith the same procedures as in Example 221, using(R)—N-(4-fluoro-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amineprepared in Example 320.

Example 334

The product in the form of pale yellow oil was prepared in accordancewith the same procedures as in Example 221, using(R)—N-(4-methyl-3-nitrophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amineprepared in Example 321.

Example 335

A solution of(S)-3-(4-{3-[2-(benzyloxy)ethylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrile(60 mg, 0.13 mmol) prepared in Example 145, palladium/charcoal (12 mg,10 wt %) and a catalytic amount of conc. HCl in methanol (6.0 ml) wasstirred at room temperature under hydrogen atmosphere overnight and thenfiltered through a celite pad. The resulting filtrate was concentratedunder reduced pressure. The resulting residue was dissolved in ethylacetate (1 ml) and then hydrogen chloride gas was added thereto. Thereaction mixture was stirred at room temperature for 1 hour and thenfiltered to give 39.0 mg of the product as a white solid.

Example 336

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)-5-{4-butyl-6-[2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidin-2-ylamino}-2-methylbenzonitrileprepared in Example 229.

Examples 337 and 338

The products of Examples 337 and 338 were prepared in accordance withthe same procedures as in Example 223, usingN¹-(4-butyl-6-chloropyrimidin-2-yl)-3-nitrobenzene-1,4-diamine preparedin Preparation 16; and (S)—N-(pyrrolidin-3-yl)acetamide or(3S)-(−)-3-(methylamino)pyrrolidine.

Example 339

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)-3-(4-{3-[(1H-pyrrol-2-yl)methylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrileprepared in Example 111.

Example 340

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 168, using(S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidineprepared in Preparation 2 and 2-nitro-1,4-phenylenediamine.

Example 341

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 118, using(S)-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanolprepared in Example 208.

Example 342

A mixture of (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate (30 mg, 0.09mmol) prepared in Preparation 21, 5-(trifluoromethyl)benzene-1,3-diamine(19.4 mg, 0.11 mmol), and n-butanol (1 ml) was refluxed under stirringovernight. The reaction mixture was cooled to room temperature and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (dichloromethane/methanol=20/1)and then dissolved in ethyl acetate (2 ml). Hydrogen chloride gas wasadded to the solution. The reaction mixture was stirred at roomtemperature for 1 hour and then filtered to give 11.1 mg of the productas a white solid.

Examples 343 to 361

The products of Examples 343 to 361 were prepared in accordance with thesame procedures as in Example 342, using (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate prepared inPreparation 21; and 2-methylbenzene-1,4-diamine prepared in Preparation23, 4-chloro-3-nitroaniline, 3-(methylthio)aniline, 6-aminoindole,3-(trifluoromethyl)aniline, 5-chloro-2-methylaniline,4-amino-2-chlorotoluene, 3-nitroaniline, 4-methyl-3-nitroaniline,2-(trifluoromethyl)benzene-1,4-diamine, 5-amino-2-fluorobenzonitrile,5-amino-2-methylbenzonitrile, 2,5-diaminobenzonitrile prepared inPreparation 19, (5-amino-2-methoxyphenyl)carbamic acid benzyl ester,4-fluoro-3-(trifluoromethyl)aniline, 4-fluoro-3-nitroaniline,2-nitro-1,4-phenylenediamine, 3,5-bis(trifluoromethyl)aniline or3,5-dimethoxyaniline.

Example 362

A solution of (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate (30 mg, 0.09mmol) prepared in Preparation 21, 3,5-diaminobenzonitrile (14.6 mg, 0.11mmol) in butanol (1 ml) was refluxed under stirring overnight. Thereaction mixture was cooled to room temperature and then concentratedunder reduced pressure. Hydrochloric acid was added at 0° C. to theresulting residue. The suspension was stirred at room temperature for 2hours and then filtered. The resulting solid was washed with ethylacetate. The solid was dissolved in dichloromethane (10 ml) and then anaqueous saturated solution of sodium bicarbonate was added thereto. Thesolution was stirred for 30 minutes and then extracted withdichloromethane. The organic layer was dried on anhydrous magnesiumsulfate and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1) to give 11.7 mg of the titled compound as awhite solid.

Example 363

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 362, using (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-ylcarbamate prepared inPreparation 21 and 3-aminobenzenesulfonamide.

Example 364

Palladium/charcoal (25 mg, 10 wt %) was added to a solution of(S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine(20 mg, 0.06 mmol) prepared in Example 32 in methanol (2 ml). Thereaction mixture was stirred at room temperature under hydrogenatmosphere (30 bar) for 3 hours and then filtered through a celite pad.The resulting filtrate was concentrated under reduced pressure. Theresulting residue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1) to give 4.4 mg of the product as a paleyellow solid.

Example 365

The product (4.4 mg) in the form of pale yellow solid was prepared inaccordance with the same procedures as in Example 364, using(S)—N-(4-fluoro-3-nitrophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amineprepared in Example 31.

Example 366

The product (7.2 mg) in the form of pale yellow solid was prepared inaccordance with the same procedures as in Example 364, using(S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amineprepared in Example 40.

Example 367 <Step 1> (S)-benzyl2-methoxy-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}phenylcarbamate

The titled compound (15 mg) in the form of pale yellow oil was preparedin accordance with the same procedures as in Example 27, using(S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidineprepared in Preparation 2 and (5-amino-2-methoxyphenyl)carbamic acidbenzyl ester.

<Step 2>(S)-4-methoxy-N¹-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine

The titled compound (7.8 mg) in the form of pale yellow solid wasprepared in accordance with the same procedures as in Example 364, using(S)-benzyl2-methoxy-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}phenylcarbamateprepared in Step 1.

Example 368

The titled compound in the form of pale yellow oil was prepared inaccordance with the same procedures as in Example 217, using(S)-2-chloro-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidineprepared in Preparation 2 and 1-acetyl-6-aminoindoline.

Example 369

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 364, using(S)-4-(3-aminopyrrolidin-1-yl)-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-aminedihydrochloride prepared in Example 351.

Example 370 <Step 1>(S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine

The titled compound in the form of pale yellow solid was prepared inaccordance with the same procedures as in Example 364, using(S)-4-(3-aminopyrrolidin-1-yl)-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-aminedihydrochloride prepared in Example 358.

<Step 2>(S)—N¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diaminedihydrochloride

The titled compound in the form of pale yellow solid was prepared inaccordance with the same procedures as in Example 118, usingN¹-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamineprepared in Step 1.

Example 371

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 118, using(S)-3-amino-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-amino]benzonitrileprepared in Example 362.

Example 372

Cyclopropanecarboxaldehyde (6.51 ml, 0.09 mmol) was added to a solutionof(S)-4-(3-aminopyrrolidin-1-yl)-N-(4-chloro-3-nitrophenyl)-6-propylpyrimidin-2-aminedihydrochloride (30 mg, 0.07 mmol) prepared in Example 344 in methanol(1 ml). The reaction mixture was stirred at room temperature for 30minutes and then sodium cyanoborohydride (6.84 mg, 0.11 mmol) was addedthereto. The reaction mixture was stirred at room temperature overnightand then a 1N hydrochloric acid solution was added thereto. The reactionmixture was stirred for 30 minutes, neutralized with a 1N sodiumhydroxide solution, and then extracted with ethyl acetate. The organiclayer was dried on anhydrous magnesium sulfate, filtered, and thenconcentrated under reduced pressure. The resulting residue was purifiedwith silica gel column chromatography (ethyl acetate/methanol=20/1) togive 5.9 mg of the product as a pale yellow solid.

Example 373

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-4-(3-aminopyrrolidin-1-yl)-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-aminedihydrochloride prepared in Example 358.

Example 374

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-4-(3-aminopyrrolidin-1-yl)-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-aminedihydrochloride prepared in Example 351.

Example 375

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-4-(3-aminopyrrolidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-aminedihydrochloride prepared in Example 350.

Example 376

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitriledihydrochloride prepared in Example 353.

Example 377

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride prepared in Example 354.

Example 378

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-4-(3-aminopyrrolidin-1-yl)-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-aminedihydrochloride prepared in Example 345.

Example 379

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-4-(3-aminopyrrolidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-aminedihydrochloride prepared in Example 347.

Example 380

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-4-(3-aminopyrrolidin-1-yl)-N-(5-chloro-2-methylphenyl)-6-propylpyrimidin-2-aminedihydrochloride prepared in Example 348.

Example 381

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-4-(3-aminopyrrolidin-1-yl)-N-(3-chloro-4-methylphenyl)-6-propylpyrimidin-2-aminedihydrochloride prepared in Example 349.

Example 382

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 372, using(S)-4-(3-aminopyrrolidin-1-yl)-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-aminedihydrochloride prepared in Example 357.

Example 383

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 364, using(S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amineprepared in Example 374.

Example 384

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 364, using(S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(3-nitrophenyl)-6-propylpyrimidin-2-amineprepared in Example 375.

Example 385

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)-5-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-fluorobenzonitrileprepared in Example 376.

Example 386

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 118, using(S)-4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amineprepared in Example 374.

Example 387 <Step 1> tert-butyl1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 1, using3-(4-chloro-6-propylpyrimidin-2-ylamino)benzonitrile prepared inPreparation 3 and 3-(tert-butoxycarbonylamino)pyrrolidine.

<Step2>3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 47, using tert-butyl1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamateprepared in Step 1.

<Step3>3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 372, using3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitriledihydrochloride prepared in Step 2.

<Step4>3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitriledihydrochloride

The titled compound in the form of white solid was prepared inaccordance with the same procedures as in Example 118, using3-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrileprepared in Step 3.

Examples 388 to 392

The products of Examples 388 to 392 were prepared in accordance with thesame procedures as in Example 1, using4-chloro-6-ethyl-N-(4-fluorophenyl)pyrimidin-2-amine prepared inPreparation 9; and L-prolinol, (3S)-(−)-3-acetamidopyrrolidine,(S)-2-(methoxymethyl)pyrrolidine, 2-methylpyrrolidine, or(3S)-(−)-3-(ethylamino)pyrrolidine.

Example 393

A solution of(R)-3-[4-(3-hydroxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile(30 mg, 0.09 mmol) prepared in Example 57, phenol (13.1 mg, 0.14 mmol),and cyanomethylenetributylphosphorane (37 μl, 0.14 mmol) in toluene (0.5mol) was stirred in a microwave reactor (400 W) for 1 hour. The reactionmixture was cooled to room temperature and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (dichloromethane/methanol=100/1) to give 4.0 mg ofthe product as pale yellow oil.

Example 394

The product was prepared in accordance with the same procedures as inExample 118, using(S)—N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-3-yl)acetamideprepared in Example 77.

Example 395

A catalytic amount of palladium/charcoal was added to a solution of(S)-benzyl2-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylamino}-2-oxoethylcarbamate(120 mg, 0.2 mmol) prepared in Example 165 in methanol (3 ml). Thereaction mixture was stirred under hydrogen atmosphere at roomtemperature overnight. The reaction mixture was filtered through acelite pad. The resulting filtrate was concentrated under reducedpressure to give 21.2 mg of the product as colorless oil.

Example 396

The product was prepared in accordance with the same procedures as inExample 118, using(S)-3-(4-{3-[4-(dimethylamino)benzylamino]pyrrolidin-1-yl}-6-propylpyrimidin-2-ylamino)benzonitrileprepared in Example 110.

Example 397

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)-2-fluoro-5-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrileprepared in Example 214.

Example 398

The product in the form of pale red solid was prepared in accordancewith the same procedures as in Example 118, using(S)-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanolprepared in Example 212.

Example 399

The product in the form of pale red solid was prepared in accordancewith the same procedures as in Example 221, using(S)-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl]methanolprepared in Example 210.

Example 400

The product in the form of pale red solid was prepared in accordancewith the same procedures as in Example 221, using(S)-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanolprepared in Example 208.

Example 401

The product in the form of pale red solid was prepared in accordancewith the same procedures as in Example 221, using(S)-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanolprepared in Example 196.

Example 402

Dess-Martin periodinane (449 mg, 1.06 mmol) was added at roomtemperature to a solution of(S)-3-{4-[2-(hydroxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile(238 mg, 0.71 mmol) prepared in Example 194 in dichloromethane (3.5 ml),and then stirred for 4 hours. Dess-Martin periodinane (449 mg, 1.06mmol) was further added at room temperature to the reaction mixture,which was then stirred overnight. The reaction mixture was diluted withethyl ether, washed with an aqueous saturated solution of sodiumbicarbonate, dried on anhydrous sodium sulfate, and then concentratedunder reduced pressure. The resulting residue was purified with silicagel column chromatography (n-hexane/ethyl acetate=1/1) to give 154 mg ofthe product as pale yellow oil.

Example 403

A solution of(S)-3-[4-(2-formylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile(20 mg, 0.06 mmol) prepared in Example 402 and methylamine hydrochloride(4.8 mg, 0.07 mmol) in methanol (0.5 ml) was stirred at room temperaturefor 30 minutes. Sodium triacetoxyborohydride (25.3 mg, 0.12 mmol) andacetic acid (5.1 μl, 0.09 mmol) were added to the reaction mixture,which was then stirred at room temperature overnight. An aqueoussaturated solution of sodium bicarbonate was added to the reactionmixture, which was then extracted with dichloromethane. The organiclayer was dried on anhydrous sodium sulfate and then concentrated underreduced pressure. The resulting residue was purified with silica gelcolumn chromatography (ethyl acetate/methanol=1/1) to give 7 mg of theproduct as colorless oil.

Examples 404 to 407

The products of Examples 404 to 407 were prepared in accordance with thesame procedures as in Example 403, using(S)-3-[4-(2-formylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrileprepared in Example 402; and cyclobutylamine hydrochloride,4-fluorobenzylamine, n-propylamine, or ethanolamine.

Example 408

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 118, using ExampleN-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 294.

Example 409

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 118, usingN-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 295.

Example 410

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 118, usingN-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 297.

Example 411

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 118, using(R)—N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamineprepared in Example 328.

Example 412

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 118, using(R)—N¹-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamineprepared in Example 323.

Example 413

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 118, using(S)-5-{4-[3-(cyclopropylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrileprepared in Example 377.

Examples 414 to 421

The products of Examples 414 to 421 were prepared in accordance with thesame procedures as in Example 84, using(S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride prepared in Example 354; and propionaldehyde,3-(methylthio)propionaldehyde, pyrrole-2-carboxaldehyde,4-hydroxybenzaldehyde, acetone, cyclobutanone, cyclopentanone, orcyclohexanone.

Example 422

A solution of(S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride (20 mg, 0.05 mmol) prepared in Example 354 and pentanal(4.3 mg, 0.05 mmol) in methanol (1 ml) was stirred at room temperaturefor 30 minutes and then sodium cyanoborohydride (9.4 mg, 0.15 mmol) wasadded thereto. The reaction mixture was stirred at room temperature for3 hours and then an aqueous saturated solution of sodium bicarbonate wasadded thereto to terminate the reaction. The reaction mixture wasextracted with ethyl acetate. The resulting organic layer was dried onanhydrous sodium sulfate, filtered, and then concentrated. The resultingresidue was purified with silica gel column chromatography(n-hexane/ethyl acetate=1/1), and then dissolved in ethyl acetate (1ml). Hydrogen chloride gas was added to the solution. The reactionmixture was stirred at room temperature for 1 hour and then filtered togive 8 mg of the product as a white solid.

Examples 423 and 424

The products of Examples 423 and 424 were prepared in accordance withthe same procedures as in Example 422, using(S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride prepared in Example 354; and pivaldehyde or4,5-dimethylfuran-2-carboxaldehyde.

Examples 425 to 430

The products of Examples 425 to 430 were prepared in accordance with thesame procedures as in Example 61, using(S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride prepared in Example 354; and propionic acid,2-phenylacetic acid, 2-(piperidin-1-yl)acetic acid,2-(pyridin-3-yl)acetic acid, 2-(pyridin-4-yl)acetic acid, or2-(thiophene-2-yl)acetic acid.

Example 431

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 124, using(S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride prepared in Example 354 and methanesulfonyl chloride.

Example 432

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methanesulfonamideprepared in Example 431.

Example 433

Ethyl isocyanate (7.1 mg, 0.1 mmol) was slowly added at room temperatureto a solution of(S)-5-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitriledihydrochloride (20 mg, 0.05 mmol) prepared in Example 354 anddiisopropylethylamine (0.03 ml, 0.14 mmol) in dichloromethane (1 ml).The reaction mixture was stirred at room temperature for 30 minutes.Water was added to the reaction mixture, which was then extracted withdichloromethane. The separated organic layer was dried on anhydroussodium sulfate, filtered, and then concentrated under reduced pressure.The resulting residue was purified with silica gel column chromatography(ethyl acetate) and then dissolved in ethyl acetate (2 ml). Hydrogenchloride gas was added to the solution. The reaction mixture was stirredat room temperature for 2 hours and then filtered to give 6 mg of theproduct as a white solid.

Example 434

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 84, using(R)-3-{4-[3-(aminomethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitriledihydrochloride prepared in Example 179 and acetaldehyde.

Example 435

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)-5-{4-[3-(isopropylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrileprepared in Example 418.

Examples 436 to 446

The products of Examples 436 to 446 were prepared in accordance with thesame procedures as in Example 26, using(S)—N-[1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl]acetamideprepared in Preparation 24; and 4-methyl-3-nitroaniline,4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline,3,5-diaminobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine,2-(trifluoromethyl)benzene-1,4-diamine,4-fluoro-3-trifluoromethylphenylamine, 5-amino-2-fluorobenzonitrile,4-fluoro-1,3-phenylenediamine, 4-chloro-1,3-phenylenediamine, or2,5-diaminobenzonitrile prepared in Preparation 19.

Example 447

A solution of (S)-tert-butyl1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate (85mg, 0.23 mmol) prepared in Preparation 25 and 2,5-diaminobenzonitrile(34 mg, 0.25 mmol) prepared in Preparation 19 in n-butanol (0.5 ml) wasstirred at 130° C. for 3 hours. The reaction mixture was cooled to roomtemperature and then concentrated under reduced pressure. The resultingresidue was purified with silica gel column chromatography(dichloromethane/methanol=20/1) and then dissolved in ethylacetate/methanol (1 ml/1 ml). The resulting solution was saturated withhydrogen chloride gas and then filtered to give 46.7 mg of the productas a white solid.

Examples 448 to 457

The products of Examples 448 to 457 were prepared in accordance with thesame procedures as in Example 447, using (S)-tert-butyl1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamateprepared in Preparation 25; and 4-methyl-3-nitroaniline,4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline,3,5-diaminobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine,2-(trifluoromethyl)benzene-1,4-diamine,4-fluoro-3-trifluoromethylphenylamine, 5-amino-2-fluorobenzonitrile,4-fluoro-1,3-phenylenediamine, or 4-chloro-1,3-phenylenediamine.

Examples 458 to 471

The products of Examples 458 to 471 were prepared in accordance with thesame procedures as in Example 447, using (S)-tert-butyl1-(6-butyl-2-chloropyrimidin-4-yl)pyrrolidin-3-yl(ethyl)carbamateprepared in Preparation 26; and 2,5-diaminobenzonitrile prepared inPreparation 19, 3-aminobenzonitrile, 5-amino-2-methylbenzonitrile,2-nitro-1,4-phenylenediamine, 4-methyl-3-nitroaniline,4-fluoro-3-nitroaniline, 4-chloro-3-nitroaniline,3,5-diaminobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine,2-(trifluoromethyl)benzene-1,4-diamine,4-fluoro-3-trifluoromethylphenylamine, 5-amino-2-fluorobenzonitrile,4-fluoro-1,3-phenylenediamine, or 4-chloro-1,3-phenylenediamine.

Example 472

A mixture of(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]-2-hydroxyacetamide(20 mg, 0.07 mmol) prepared in Preparation 27 and5-amino-2-methylbenzonitrile (10.6 mg, 0.08 mmol) in n-butanol (0.5 ml)was stirred in a microwave reactor (600 W) for 1 hour. The reactionmixture was concentrated under reduced pressure. The resulting residuewas purified with silica gel column chromatography(dichloromethane/methanol=20/1) to give 5.9 mg of the product as yellowoil.

Examples 473 to 481

The products of Examples 473 to 481 were prepared in accordance with thesame procedures as in Example 472, using(S)—N-[1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl]-2-hydroxyacetamideprepared in Preparation 27; and 5-amino-2-fluorobenzonitrile,3,5-diaminobenzonitrile, 5-(trifluoromethyl)benzene-1,3-diamine,2-(trifluoromethyl)benzene-1,4-diamine,4-fluoro-3-trifluoromethylphenylamine, 4-fluoro-1,3-phenylenediamine,4-chloro-1,3-phenylenediamine, 2-chloro-4-aminotoluene, or4-methyl-3-(trifluoromethyl)aniline.

Example 482

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamideprepared in Example 474.

Example 483

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-hydroxyacetamideprepared in Example 472.

Example 484

A solution of (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamate (0.2g, 0.56 mmol) prepared in Preparation 28, 4-fluorobenzene-1,3-diamine(0.1 g, 0.61 mmol), and diisopropylethylamine (0.2 ml, 1.12 mmol) inn-butanol (2 ml) was stirred at 130° C. overnight. The reaction mixturewas cooled to room temperature and then concentrated under reducedpressure. The resulting residue was purified with silica gel columnchromatography (dichloromethane/ethyl acetate=20/1) and then dissolvedin ethyl acetate (2 ml). Hydrogen chloride gas was added to thesolution. The reaction mixture was stirred at room temperature for 1hour and then filtered to give 0.1 g of the product as a white solid.

Examples 485 to 487

The products of Examples 485 to 487 were prepared in accordance with thesame procedures as in Example 484, using (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(methyl)carbamateprepared in Preparation 28; and 3,5-diaminobenzonitrile,2,5-diaminobenzonitrile prepared in Preparation 19, or5-(trifluoromethyl)-1,3-phenylenediamine.

Examples 488 to 489

The products of Examples 488 to 489 was prepared in accordance with thesame procedures as in Example 484, using (S)-tert-butyl1-(2-chloro-6-propylpyrimidin-4-yl)pyrrolidin-3-yl(ethyl)carbamateprepared in Preparation 29; and 2-(trifluoromethyl)-1,4-phenylenediamineor 2,5-diaminobenzonitrile prepared in Preparation 19.

Examples 490 and 491

The products of Examples 490 and 491 were prepared in accordance withthe same procedures as in Example 172, using4-chloro-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amineprepared in Preparation 30; and (3S)-(−)-3-(methylamino)pyrrolidine or(3S)-(−)-3-(ethylamino)pyrrolidine.

Example 492

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 228.

Example 493

The product in the form of white solid was prepared in accordance withthe same procedures as in Example 118, using(S)—N-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamideprepared in Example 292.

Example 494

The product in the form of pale yellow solid was prepared in accordancewith the same procedures as in Example 395, using(S)—N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamidehydrochloride prepared in Example 286.

The compounds of Examples 1 to 494 and the NMR spectrum data thereof areshown in Tables 1-1 to 1-51 below.

TABLE 1-1 Example Compound NMR Spectrum 1 N-(4-fluorophenyl)-4-propyl-¹H-NMR(400 MHz, CDCl₃) δ 7.70-7.60(m, 2H), 6.97(t,6-(pyrrolidin-1-yl)pyrimidin- 2H), 5.68(s, 1H), 3.70-3.20(m, 4H),2.46(t, 2H), 2.10- 2-amine 1.90(m, 4H), 1.80-1.60(m, 2H), 0.97(t, 3H) 2(S)-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), 6.99(t,fluorophenylamino)-6- 2H), 6.75(brs, 1H), 5.74(s, 1H), 4.38(brs, 1H),3.80- propylpyrimidin-4- 3.60(m, 2H), 3.50-3.40(m, 1H), 3.40-3.30(m,1H), 2.48(t, yl]pyrrolidin-2-yl}methanol 2H), 2.10-1.90(m, 3H),1.80-1.60(m, 3H), 0.98(t, 3H) 3 1-[2-(4-fluorophenylamino)- ¹H-NMR(400MHz, CDCl₃) δ 7.60-7.50(m, 2H), 6.97(t, 6-propylpyrimidin-4- 2H),6.84(brs, 1H), 5.70(s, 1H), 4.62(brs, 1H), 3.63(brs, yl]pyrrolidin-3-ol4H), 2.46(t, 2H), 2.20-2.00(m, 2H), 1.71(q, 2H), 0.98(t, 3H) 4(R)-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.55-7.45(m, 2H), 6.98(t,fluorophenylamino)-6- 2H), 6.83(brs, 1H), 5.74(s, 1H), 4.35(brs, 1H),3.70- propylpyrimidin-4- 3.55(m, 2H), 3.50-3.40(m, 1H), 3.40-3.30(m,1H), 2.47(t, yl]pyrrolidin-2-yl}methanol 2H), 2.10-1.90(m, 3H),1.80-1.60(m, 3H), 0.98(t, 3H) 5 {1-[2-(4-fluorophenylamino)- ¹H-NMR(400MHz, CDCl₃) δ 7.55-7.45(m, 2H), 6.98(t, 6-propylpyrimidin-4- 2H),6.83(brs, 1H), 5.74(s, 1H), 4.35(brs, 1H), 3.70-yl]pyrrolidin-2-yl}methanol 3.55(m, 2H), 3.50-3.40(m, 1H), 3.40-3.30(m,1H), 2.47(t, 2H), 2.10-1.90(m, 3H), 1.80-1.60(m, 3H), 0.98(t, 3H) 6N-(4-fluorophenyl)-4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H),6.97(t, methylpyrrolidin-1-yl)-6- 2H), 6.83(brs, 1H), 5.68(s, 1H),4.20(brs, 1H), 3.55(brs, propylpyrimidin-2-amine 1H), 3.38(brs, 1H),2.45(t, 2H), 2.10-1.90(m, 3H), 1.80- 1.65(m, 3H), 1.23(d, 3H), 0.98(t,3H) 7 (S)-N-(4-fluorophenyl)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m,2H), 6.97(t, (methoxymethyl)pyrrolidin- 2H), 6.86(brs, 1H), 5.73(s, 1H),4.30-4.10(brs, 1H), 1-yl]-6-propylpyrimidin-2- 3.66(brs, 1H), 3.49(brs,1H), 3.36(s, 3H), 3.30-3.15(m, amine 2H), 2.46(t, 2H), 2.10-1.85(m, 4H),1.71(q, 2H), 0.98(t, 3H) 8 (R)-N-(4-fluorophenyl)-4-[2- ¹H-NMR(400 MHz,CDCl₃) δ 7.65-7.55(m, 2H), 6.97(t, (methoxymethyl)pyrrolidin- 2H),6.86(brs, 1H), 5.73(s, 1H), 4.30-4.10(brs, 1H),1-yl]-6-propylpyrimidin-2- 3.66(brs, 1H), 3.49(brs, 1H), 3.36(s, 3H),3.30-3.15(m, amine 2H), 2.46(t, 2H), 2.10-1.85(m, 4H), 1.71(q, 2H),0.98(t, 3H) 9 (S)-1-[2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.65-7.55(m, 2H),6.97(t, fluorophenylamino)-6- 2H), 5.90(s, 1H), 4.60-4.40(m, 1H),3.75-3.60(m, 1H), propylpyrimidin-4- 3.55-3.35(m, 1H), 2.47(t, 2H),2.30-2.20(m, 1H), 2.15- yl]pyrrolidin-2-carboxamide 1.95(m, 3H), 1.72(q,2H), 0.98(t, 3H) 10 N-{1-[2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.70-7.60(m,2H), 6.98(t, fluorophenylamino)-6- 2H), 5.81(s, 1H), 4.44(t, 1H),3.80-3.30(m, 4H), 2.45(t, propylpyrimidin-4- 2H), 2.30-2.20(m, 1H),2.05-1.95(m, 1H), 1.94(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.71(q, 2H),0.97(t, 3H)

TABLE 1-2 Example Compound NMR Spectrum 11 (R)-N-{1-[2-(4- ¹H-NMR(400MHz, CDCl₃) δ 7.70-7.60(m, 2H), 6.98(t, fluorophenylamino)-6- 2H),5.79(brs, 1H), 5.68(s, 1H), 4.65-4.55(m, 1H), 3.80- propylpyrimidin-4-3.70(m, 1H), 3.65-3.45(m, 3H), 2.46(t, 2H), 2.00(s, 3H),yl]pyrrolidin-3-yl}acetamide 1.80-1.60(m, 2H), 0.97(t, 3H) 122,2,2-trifluoro-N-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H),6.99(t, fluorophenylamino)-6- 2H), 6.80(brs, 1H), 6.54(brs, 1H), 5.70(s,1H), 4.70- propylpyrimidin-4- 4.60(m, 1H), 3.85-3.75(m, 1H),3.70-3.30(m, 3H), 2.48(t, yl]pyrrolidin-3-yl}acetamide 2H), 2.40-2.30(m,1H), 2.15-2.05(m, 1H), 1.80-1.65(m, 2H), 0.98(t, 3H) 134-[3-(ethylamino)pyrrolidin- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H),6.96(t, 1-yl]-N-(4-fluorophenyl)-6- 2H), 6.92(brs, 1H), 5.67(s, 1H),3.47(t, 2H), 2.72(q, 2H), propylpyrimidin-2-amine 2.45(t, 2H),2.25-2.10(m, 1H), 1.90-1.80(m, 1H), 1.71(q, 2H), 1.15(t, 3H), 0.99(t,3H) 14 4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.96(t,(dimethylamino)pyrrolidin-1- 2H), 6.88(brs, 1H), 5.68(s, 1H),4.00-3.50(m, 2H), 3.50- yl]-N-(4-fluorophenyl)-6- 3.30(m, 1H),3.30-3.10(m, 1H), 2.85-2.70(m, 1H), 2.46(t, propylpyrimidin-2-amine 2H),2.31(s, 6H), 2.20-2.10(m, 1H), 1.90-1.80(m, 1H), 1.72(q, 2H), 0.97(t,3H) 15 (S)-N-(4-fluorophenyl)-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.70-7.60(m,2H), 6.97(t, propyl-6-[2-(pyrrolidin-1- 2H), 5.72(s, 1H), 3.60-3.20(m,2H), 3.10-2.60(m, 6H), ylmethyl)pyrrolidin-1- 2.51(t, 2H), 2.40-2.20(m,1H), 2.10-2.00(m, 4H), 2.00- yl]pyrimidin-2-amine 1.80(m, 4H), 1.75(q,2H), 0.99(t, 3H) 16 (S)-N-(4-fluorophenyl)-4-{2- ¹H-NMR(400 MHz, CDCl₃)δ 7.60-7.50(m, 2H), 7.20- [(phenylamino)methyl]pyrrolidin- 7.10(m, 2H),6.93(t, 2H), 6.79(brs, 1H), 6.65(t, 1H), 6.50- 1-yl}-6-propylpyrimidin-6.40(m, 2H), 5.72(s, 1H), 4.70-4.40(m, 1H), 3.60-3.20(m, 2-amine 3H),3.20-3.10(m, 1H), 2.46(t, 2H), 2.20-1.90(m, 4H), 1.71(q, 2H), 0.98(t,3H) 17 (S)-N-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), 7.05-fluorophenylamino)-6- 6.90(m, 3H), 6.08(brs, 1H), 5.66(s, 1H), 4.56(brs,1H), propylpyrimidin-4- 3.80-3.20(m, 4H), 2.45(t, 2H), 2.30-2.15(m, 1H),1.98(s, yl]pyrrolidin-3-yl}acetamide 3H), 2.00-1.90(m, 1H), 1.70(q, 2H),0.96(t, 3H) 18 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H),6.96(t, (ethylamino)pyrrolidin-1-yl]- 2H), 6.92(brs, 1H), 5.67(s, 1H),3.47(t, 2H), 2.72(q, 2H), N-(4-fluorophenyl)-6- 2.45(t, 2H),2.25-2.10(m, 1H), 1.90-1.80(m, 1H), 1.71(q, propylpyrimidin-2-amine 2H),1.14(t, 3H), 0.97(t, 3H) 19 (S)-tert-butyl 1-[2-(4- ¹H-NMR(400 MHz,CDCl₃) δ 7.65-7.55(m, 2H), 6.97(t, fluorophenylamino)-6- 2H), 6.86(brs,1H), 5.68(s, 1H), 4.72(brs, 1H), 4.34(brs, propylpyrimidin-4- 1H),3.80-3.20(m, 4H), 2.46(t, 2H), 2.30-2.20(m, 1H),yl]pyrrolidin-3-ylcarbamate 2.05-1.90(m, 1H), 1.71(q, 2H), 1.46(s, 9H),0.97(t, 3H) 20 4-(3-aminopyrrolidin-1-yl)- ¹H-NMR(400 MHz, CD₃OD) δ7.70-7.60(m, 2H), 6.98(t, N-(4-fluorophenyl)-6- 2H), 5.84(s, 1H),3.90-3.35(m, 5H), 2.46(t, 2H), 2.35- propylpyrimidin-2-amine 2.25(m,1H), 2.00-1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H)

TABLE 1-3 Example Compound NMR Spectrum 21 4-[3- ¹H-NMR(400 MHz, CDCl₃)δ 7.65-7.55(m, 2H), 7.05- (diethylamino)pyrrolidin-1- 6.90(m, 3H),5.68(s, 1H), 4.00-3.10(m, 5H), 2.80-2.60(m, yl]-N-(4-fluorophenyl)-6-4H), 2.46(t, 2H), 2.25-2.15(m, 1H), 1.90-1.80(m, 1H),propylpyrimidin-2-amine 1.72(q, 2H), 1.06(t, 6H), 0.98(t, 3H) 22(S)-N-(4-fluorophenyl)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.70-7.60(m, 2H),7.20(brs, (methylamino)pyrrolidin-1- 1H), 6.97(t, 2H), 5.68(s, 1H),3.80-3.10(m, 5H), 2.49(s, yl]-6-propylpyrimidin-2- 3H), 2.47(t, 2H),2.20-2.10(m, 1H), 1.90-1.80(m, 1H), amine 1.71(q, 2H), 0.98(t, 3H) 23N-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.65-7.55(m, 2H), 6.98(t,fluorophenylamino)-6- 2H), 6.88(brs, 1H), 5.69(s, 1H), 5.39(t, 1H),3.80-3.20(m, propylpyrimidin-4- 4H), 2.94(s, 3H), 2.47(t, 2H),2.30-2.20(m, 2H), 2.14(s, yl]pyrrolidin-3-yl}-N- 3H), 1.72(q, 2H),0.98(t, 3H) methylacetamide 24 (S)-1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ7.65-7.55(m, 2H), 6.97(t, fluorophenylamino)-6- 2H), 6.85(brs, 1H),5.68(s, 1H), 4.62(brs, 1H), 3.80- propylpyrimidin-4- 3.30(m, 4H),2.46(t, 2H), 2.20-2.00(m, 2H), 1.71(q, 2H), yl]pyrrolidin-3-ol 0.97(t,3H) 25 4-[3-(ethylamino)pyrrolidin- ¹H-NMR(400 MHz, CD₃OD) δ7.65-7.55(m, 2H), 7.17(t, 1-yl]-N-(4-fluorophenyl)-6- 2H), 6.28(s, 1H),4.20-4.00(m, 2H), 4.00-3.80(m, 2H), propylpyrimidin-2-amine 3.80-3.70(m,1H), 3.25-3.10(m, 2H), 2.68(t, 2H), 2.60- dihydrochloride 2.45(m, 1H),2.40-2.20(m, 1H), 1.79(t, 2H), 1.45-1.30(m, 3H), 1.07(t, 3H) 26(S)-N-{4-[2- ¹H-NMR(400 MHz, CD₃OD) δ 7.61(s, 1H), 7.55(d, 1H),(methoxymethyl)pyrrolidin- 7.26(s, 1H), 7.04(d, 1H), 6.45(s, 1H),6.10(s, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 4.43(brs, 1H), 3.60(brs,1H), 3.48(brs, 1H), 3.50-3.40(m, 1H-indol-6-amine 2H), 3.10(s, 3H),2.59(t, 2H), 2.25-1.95(m, 4H), 1.74(q, hydrochloride 2H), 1.04(t, 3H) 27(S)-N-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.10-8.00(m, 2H), 7.35-(methoxymethyl)pyrrolidin- 7.25(m, 1H), 7.17(s, 1H), 6.90-6.80(m, 1H),6.49(s, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 5.69(brs, 1H), 3.80-3.60(m,2H), 3.60-3.40(m, 2H), 1H-indol-5-amine 3.33(s, 3H), 3.30-3.20(m, 1H),2.46(t, 2H), 2.10-1.90(m, 4H), 1.73(q, 2H), 0.99(t, 3H) 28 (S)-4-[2-¹H-NMR(400 MHz, CDCl₃) δ 7.60-7.50(m, 2H), 6.90-(methoxymethyl)pyrrolidin- 6.80(m, 2H), 6.74(brs, 1H), 5.70(s, 1H),4.35(brs, 1H), 1-yl]-N-(4-methoxyphenyl)- 3.79(s, 3H), 3.80-3.60(m, 1H),3.50-3.40(m, 1H), 3.36(s, 6-propylpyrimidin-2-amine 3H), 3.30-3.20(m,2H), 2.50-2.40(m, 2H), 2.20-1.90(m, 4H), 1.80-1.65(m, 2H), 1.00-0.90(m,3H) 29 (S)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.50-7.40(m, 1H), 7.20-(methoxymethyl)pyrrolidin- 7.10(m, 2H), 6.87(brs, 1H), 6.51(d, 1H),5.74(s, 1H), 1-yl]-N-(3-methoxyphenyl)- 3.81(s, 3H), 3.80-3.60(m, 2H),3.60-3.40(m, 1H), 3.36(s, 6-propylpyrimidin-2-amine 3H), 3.30-3.20(m,2H), 2.46(t, 2H), 2.10-1.90(m, 4H), 1.72(q, 2H), 0.98(t, 3H) 30(S)-N-(3-chlorophenyl)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.95(s, 1H),7.34(d, 1H), (methoxymethyl)pyrrolidin- 7.17(t, 1H), 7.00-6.80(m, 2H),5.76(brs, 1H), 4.50- 1-yl]-6-propylpyrimidin-2- 4.30(m, 1H),3.80-3.30(m, 4H), 3.37(s, 3H), 2.47(t, 2H), amine 2.20-1.90(m, 4H),1.72(q, 2H), 0.98(t, 3H)

TABLE 1-4 Example Compound NMR Spectrum 31 (S)-N-(4-fluoro-3- ¹H-NMR(400MHz, CDCl₃) δ 9.00-8.70(m, 1H), 7.70- nitrophenyl)-4-[2- 7.40(m, 1H),7.16(t, 1H), 7.11(brs, 1H), 5.83(brs, 1H), (methoxymethyl)pyrrolidin-4.50-4.20(m, 1H), 3.70-3.35(m, 4H), 3.36(s, 3H), 2.48(t,1-yl]-6-propylpyrimidin-2- 2H), 2.20-1.90(m, 4H), 1.72(q, 2H), 0.98(t,3H) amine 32 (S)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.75(brs, 1H), 7.48(brs,2H), (methoxymethyl)pyrrolidin- 7.37(d, 1H), 6.05(brs, 1H), 5.83(brs,1H), 4.40(brs, 1H), 1-yl]-N-(3-nitrophenyl)-6- 3.65-3.40(m, 4H), 3.36(s,3H), 2.60-2.40(m, 2H), 2.30- propylpyrimidin-2-amine 1.90(m, 4H),1.71(q, 2H), 0.98(t, 3H) 33 (S)-N-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ7.77(dd, 1H), 7.64(brs, 1H), nitrophenyl)-4-[2- 7.38(t, 1H), 7.19(brs,1H), 5.83(brs, 1H), 4.60-4.30(m, (methoxymethyl)pyrrolidin- 1H),3.70-3.40(m, 4H), 3.36(s, 3H), 2.49(t, 2H), 2.20-1-yl]-6-propylpyrimidin-2- 1.90(m, 4H), 1.73(q, 2H), 0.99(t, 3H) amine34 (S)-3-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.23(brs, 1H), 7.66(brs, 1H),(methoxymethyl)pyrrolidin- 7.34(t, 1H), 7.21(d, 1H), 7.08(brs, 1H),5.81(brs, 1H), 1-yl]-6-propylpyrimidin-2- 4.50-4.30(m, 1H), 3.70-3.40(m,4H), 3.31(s, 3H), 2.48(t, ylamino}benzonitrile 2H), 2.20-1.90(m, 4H),1.72(q, 2H), 0.99(t, 3H) 35 (S)-4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.66(br,1H), 7.40(br, 1H), (methoxymethyl)pyrrolidin- 7.19(t, 2H), 6.85(d, 1H),5.75(br, 1H), 4.37(br, 1H), 1-yl]-N-[3- 3.63(br, 2H), 3.36(s, 3H),2.48(m, 5H), 2.09(m, 2H), (methylthio)phenyl]-6- 2.00(m, 2H), 1.74(m,2H), 0.98(t, 3H) propylpyrimidin-2-amine 36 (S)-4-[2- ¹H-NMR(400 MHz,CDCl₃) δ 8.89(br, 1H), 8.45-8.20(br, (methoxymethyl)pyrrolidin- 1H),7.65(br, 1H), 7.39(t, 1H), 7.25(m, 1H), 5.78-5.62(br,1-yl]-6-propyl-N-[3- 2H), 4.49-4.05(br, 1H), 3.54(br, 3H), 3.33(br, 4H),2.55(t, (trifluoromethyl)phenyl]pyrimidin- 2H), 2.04(br, 2H), 1.81(m,2H), 1.00(t, 3H) 2-amine 37 (S)-7-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ8.03(br, 1H), 7.69(br, 1H), (methoxymethyl)pyrrolidin- 7.46(d, 1H),7.35(br, 1H), 6.12(s, 1H), 5.80(br, 1H), 4.53-1-yl]-6-propylpyrimidin-2- 3.73(br, 2H), 3.57-3.22(br, 2H), 3.40(s, 3H),2.73(br, 1H), ylamino}-4-methyl-2H- 2.50(t, 2H), 2.39(s, 3H), 2.18(m,1H), 2.05(m, 3H), chromen-2-one 1.76(m, 2H), 0.97(t, 3H) 38(S)-N-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.24(br, 1H), 8.05(br, 1H),methylphenyl)-4-[2- 6.95(d, 1H), 6.93(d, 1H), 5.76(br, 1H), 4.44(br,1H), (methoxymethyl)pyrrolidin- 3.53(br, 3H), 3.31(br, 4H), 2.55(t, 2H),2.40(s, 3H), 2.10- 1-yl]-6-propylpyrimidin-2- 2.01(m, 4H), 1.79(m, 2H),1.01(t, 3H) amine 39 (S)-N-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ8.56(br, 1H), 7.89(br, 1H), methylphenyl)-4-[2- 7.30(m, 1H), 7.11(d,1H), 5.89-5.73(br, 2H), 3.63- (methoxymethyl)pyrrolidin- 3.48(br, 3H),3.35(m, 4H), 2.53(t, 2H), 2.30(s, 3H), 2.10- 1-yl]-6-propylpyrimidin-2-2.03(m, 4H), 1.79(m, 2H), 1.00(t, 3H) amine 40 (S)-4-[2- ¹H-NMR(400 MHz,CDCl₃) δ 9.00-8.73(br, 2H), 7.52(br, (methoxymethyl)pyrrolidin- 1H),7.22(d, 1H), 5.96(br, 1H), 5.55(br, 1H), 4.55- 1-yl]-N-(4-methyl-3-4.10(br, 1H), 3.59(br, 3H), 3.33(m, 4H), 2.55(m, 4H), nitrophenyl)-6-2.60(m, 4H), 1.79(m, 2H), 1.00(t, 3H) propylpyrimidin-2-amine

TABLE 1-5 Example Compound NMR Spectrum 41 (S)-N-[4-fluoro-3- ¹H-NMR(400MHz, CDCl₃) δ 9.20(br, 1H), 8.42-8.12(br, (trifluoromethyl)phenyl]-4-1H), 7.67(br, 1H), 7.12(t, 1H), 5.78(br, 2H), 4.45-4.07(br, [2- 1H),3.50(br, 3H), 3.32(m, 4H), 2.56(t, 2H), 2.06(m, 4H),(methoxymethyl)pyrrolidin- 1.81(m, 2H), 1.00(t, 3H)1-yl]-6-propylpyrimidin-2- amine 42 (S)-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃)δ 7.93(br, 1H), 7.41(br, 1H), (methoxymethyl)pyrrolidin- 6.76(br, 1H),6.69(d, 1H), 5.72(br, 1H), 4.36(br, 1H), 1-yl]-6-propylpyrimidin-2-yl}-4.00(s, 2H), 3.55(br, 2H), 3.33(m, 5H), 2.45(t, 2H),3-(trifluoromethyl)benzene- 2.09(m, 2H), 2.00(m, 2H), 1.72(m, 2H),0.97(t, 3H) 1,4-diamine 43 (S)-2-fluoro-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃)δ 8.21(br, 1H), 8.06(br, 1H), (methoxymethyl)pyrrolidin- 7.11(t, 1H),5.80(br, 1H), 4.45(br, 1H), 3.62(m, 3H), 1-yl]-6-propylpyrimidin-2-3.37(m, 5H), 2.51(t, 2H), 2.12-2.04(m, 4H), 1.75(m, 2H),ylamino}benzonitrile 0.99(t, 3H) 44 (S)-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃)δ 8.58(br, 1H), 8.17(br, 1H), (methoxymethyl)pyrrolidin- 7.57(br, 1H),7.22(d, 1H), 5.78(br, 1H), 5.31(br, 1H), 1-yl]-6-propylpyrimidin-2-4.49-4.00(br, 1H), 3.63(m, 3H), 3.41(m, 4H), 2.55(t, 2H), ylamino}-2-2.51(s, 3H), 2.18-2.05(m, 4H), 1.77(m, 2H), 0.99(t, 3H)methylbenzonitrile 45 (S)-2-amino-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ7.92(br, 1H), 7.43(m, 1H), (methoxymethyl)pyrrolidin- 7.12(br, 1H),6.71(d, 1H), 5.75(br, 1H), 4.40(br, 1H), 1-yl]-6-propylpyrimidin-2-4.19(s, 2H), 3.53(br, 3H), 3.36(s, 5H), 2.47(t, 2H),ylamino}benzonitrile 2.21(br, 2H), 2.05(m, 2H), 1.97(m, 2H), 1.72(m,2H), 0.98(t, 3H) 46 (S)-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.72(br, 1H),8.35(br, 1H), (methoxymethyl)pyrrolidin- 7.41(br, 1H), 6.80(d, 1H),6.06(s, 2H), 5.78(br, 1H), 4.60- 1-yl]-6-propylpyrimidin-2-yl}- 4.10(br,3H), 3.54(br, 3H), 3.32(m, 3H), 2.52(t, 2H), 2.18-3-nitrobenzene-1,4-diamine 2.03(m, 2H), 1.79(m, 2H), 0.99(t, 3H) 47(S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.60-7.45(m, 2H),7.15(t, yl)-N-(4-fluorophenyl)-6- 2H), 6.30-6.20(m, 1H), 4.10-3.91(m,2H), 3.90-3.70(m, propylpyrimidin-2-amine 3H), 2.66(t, 2H), 2.60-2.40(m,1H), 2.30-2.10(m, 1H), dihydrochloride 1.80-1.65(m, 2H), 1.05(t, 3H) 48(S)-tert-butyl 1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H),7.62(brs, 1H), cyanophenylamino)-6- 7.34(t, 1H), 7.21(d, 1H), 7.01(brs,1H), 5.75(s, 1H), propylpyrimidin-4- 4.71(brs, 1H), 4.34(brs, 1H),3.80-3.20(m, 4H), 2.48(t, yl]pyrrolidin-3-ylcarbamate 2H), 2.40-2.20(m,1H), 2.10-1.90(m, 1H), 1.72(q, 2H), 1.46(s, 9H), 0.98(t, 3H) 49 3-{4-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.44(brs, 1H), 7.55(d, 1H),(diethylamino)pyrrolidin-1- 7.32(t, 1H), 7.20(d, 1H), 7.13(brs, 1H),5.74(s, 1H), 4.00- yl]-6-propylpyrimidin-2- 3.80(m, 1H), 3.70-3.10(m,4H), 2.71(d, 4H), 2.48(t, 2H), ylamino}benzonitrile 2.25-2.15(m, 1H),2.00-1.85(m, 1H), 1.72(q, 2H), 1.05(t, 6H), 0.98(t, 3H) 50 (S)-3-{4-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.57(dd, 1H),(methylamino)pyrrolidin-1- 7.32(t, 1H), 7.19(d, 1H), 7.17(brs, 1H),5.74(s, 1H), 3.90- yl]-6-propylpyrimidin-2- 3.10(m, 5H), 2.50(s, 3H),2.48(t, 2H), 2.30-2.10(m, 1H), ylamino}benzonitrile 1.90-1.85(m, 1H),1.72(q, 2H), 0.98(t, 3H)

TABLE 1-6 Example Compound NMR Spectrum 51 N-{1-[2-(3- ¹H-NMR(400 MHz,CDCl₃) δ 8.32(s, 1H), 7.61(d, 1H), cyanophenylamino)-6- 7.34(t, 1H),7.21(d, 1H), 7.02(s, 1H), 5.75(s, 1H), 5.37(t, propylpyrimidin-4- 1H),3.90-3.20(m, 4H), 2.96(s, 3H), 2.49(t, 2H), 2.30- yl]pyrrolidin-3-yl}-N-2.20(m, 2H), 2.15(s, 3H), 1.73(q, 2H), 0.98(t, 3H) methylacetamide 52(S)-3-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.55(dd, 1H),hydroxypyrrolidin-1-yl)-6- 7.32(t, 1H), 7.20(d, 1H), 7.00(brs, 1H),5.75(s, 1H), propylpyrimidin-2- 4.65(brs, 1H), 3.90-3.30(m, 4H), 2.48(t,2H), 2.20- ylamino]benzonitrile 2.00(m, 2H), 1.72(q, 2H), 0.98(t, 3H) 53(R)-3-[4-(2-methylpyrrolidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.46(brs, 1H),7.52(d, 1H), 1-yl)-6-propylpyrimidin-2- 7.40-7.25(m, 2H), 7.18(d, 1H),5.75(s, 1H), 4.50-4.10(m, ylamino]benzonitrile 1H), 3.70-3.20(m, 2H),2.47(t, 2H), 2.20-1.90(m, 3H), 1.80-1.60(m, 3H), 1.30-1.20(m, 3H),0.97(t, 3H) 54 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H),7.60(brs, 1H), cyanophenylamino)-6- 7.33(t, 1H), 7.20(d, 1H), 7.06(brs,1H), 5.80(d, 1H), propylpyrimidin-4- 5.75(s, 1H), 4.60(q, 1H),3.90-3.20(m, 4H), 2.48(t, 2H), yl]pyrrolidin-3-yl}acetamide 2.40-2.25(m,1H), 2.01(s, 3H), 1.83(brs, 1H), 1.72(q, 2H), 0.98(t, 3H) 55(S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.58(d, 1H),(ethylamino)pyrrolidin-1-yl]- 7.32(t, 1H), 7.19(d, 1H), 7.15(brs, 1H),5.74(s, 1H), 3.90- 6-propylpyrimidin-2- 3.10(m, 5H), 2.74(q, 2H),2.48(t, 2H), 2.25-2.15(m, 1H), ylamino}benzonitrile 1.90-1.80(m, 1H),1.72(q, 2H), 1.15(t, 3H), 0.98(t, 3H) 56 (R)-tert-butyl {1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.60(d, 1H), cyanophenylamino)-6-7.37(brs, 1H), 7.33(t, 1H), 7.21(d, 1H), 5.74(s, 1H), propylpyrimidin-4-4.75(brs, 1H), 3.90-3.00(m, 6H), 2.53(brs, 1H), 2.48(t, yl]pyrrolidin-3-2H), 2.20-2.10(m, 1H), 1.78(brs, 1H), 1.72(q, 2H), yl}methylcarbamate1.46(s, 9H), 0.98(t, 3H) 57 (R)-3-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ8.39(s, 1H), 7.82(d, 1H), hydroxypyrrolidin-1-yl)-6- 7.39(t, 1H),7.21(d, 1H), 5.89(s, 1H), 4.55(s, 1H), propylpyrimidin-2- 3.62(brs, 4H),2.51(t, 2H), 2.13(m, 2H), 1.73(m, 2H), ylamino]benzonitrile 0.97(t, 3H)58 (S)-3-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.41(s, 1H), 7.80(d, 1H),methoxypyrrolidin-1-yl)-6- 7.39(t, 1H), 7.21(d, 1H), 5.89(s, 1H),4.14(s, 1H), 3.60- propylpyrimidin-2- 3.55(m, 4H), 3.48(s, 3H), 2.49(t,2H), 2.19-2.11(m, 2H), ylamino]benzonitrile 1.75(m, 2H), 0.98(t, 3H) 593-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.20-8.10(m, 1H), 7.90-(methylamino)pyrrolidin-1- 7.80(m, 1H), 7.60-7.50(m, 2H), 6.35(s, 1H),4.20-3.70(m, yl]-6-propylpyrimidin-2- 5H), 2.81(s, 3H), 2.69(t, 2H),2.60-2.45(m, 1H), 2.45- ylamino}benzonitrile 2.25(m, 1H), 1.80(q, 2H),1.06(t, 3H) dihydrochloride 60 (S)-3-[4-(3-aminopyrrolidin- ¹H-NMR(400MHz, CD₃OD) δ 8.09(d, 1H), 7.90-7.80(m, 1-yl)-6-propylpyrimidin-2- 1H),7.60-7.50(m, 2H), 6.40-6.30(m, 1H), 4.20-3.70(m, ylamino]benzonitrile5H), 2.69(t, 2H), 2.60-2.45(m, 1H), 2.30-2.15(m, 1H), dihydrochloride1.80(q, 2H), 1.06(t, 3H)

TABLE 1-7 Example Compound NMR Spectrum 61 (S)-N-{1-[2-(3- ¹H-NMR(400MHz, CDCl₃) δ 8.31(brs, 1H), 7.60(brs, 1H), cyanophenylamino)-6- 7.33(t,1H), 7.20(d, 1H), 7.04(brs, 1H), 5.75(s, 1H), propylpyrimidin-4- 5.70(d,1H), 4.61(q, 1H), 3.80-3.20(m, 4H), 2.48(t, 2H),yl]pyrrolidin-3-yl}butyramide 2.40-2.25(m, 1H), 2.17(t, 2H),2.05-1.95(m, 1H), 1.80- 1.60(m, 4H), 1.00-0.90(m, 6H) 62 (S)-N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H), 7.60(brs, 1H),cyanophenylamino)-6- 7.33(t, 1H), 7.20(d, 1H), 7.09(brs, 1H), 5.75(s,1H), propylpyrimidin-4- 5.71(d, 1H), 4.65-4.55(m, 1H), 3.90-3.15(m, 4H),2.50- yl]pyrrolidin-3- 2.40(m, 3H), 2.35-2.25(m, 1H), 1.90-1.65(m, 9H),1.60- yl}cyclopentanecarboxamide 1.50(m, 2H), 1.00(t, 3H) 63(S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 9.53(brs, 1H), 8.38(brs, 1H),cyanophenylamino)-6- 7.62(brs, 1H), 7.34(t, 1H), 7.21(d, 1H), 7.02(brs,1H), propylpyrimidin-4- 5.77(s, 1H), 4.59(brs, 1H), 3.90-3.20(m, 4H),2.65(d, yl]pyrrolidin-3-yl}-3- 1H), 2.60-2.15(m, 10H), 1.90-1.85(m, 1H),1.72(q, 2H), (piperidin-1-yl)propanamide 1.50-1.25(m, 6H), 0.99(t, 3H)64 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(brs, 1H), 8.16(d, 1H),cyanophenylamino)-6- 7.79(d, 1H), 7.72(brs, 1H), 7.60-7.30(m, 5H),7.22(d, propylpyrimidin-4- 1H), 6.55(brs, 1H), 5.75(s, 1H), 4.80(q, 1H),4.00- yl]pyrrolidin-3-yl}benzamide 3.30(m, 4H), 2.53(t, 2H),2.45-2.35(m, 1H), 2.25-2.15(m, 1H), 1.73(q, 2H), 1.00(t, 3H) 65(S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.85-8.75(m, 2H), 8.31(brs,cyanophenylamino)-6- 1H), 7.60(brs, 1H), 7.33(t, 1H), 7.19(d, 1H),7.15-7.00(m, propylpyrimidin-4- 3H), 6.40(brs, 1H), 5.77(s, 1H), 4.78(q,1H), 4.00- yl]pyrrolidin-3-yl}-4- 3.30(m, 4H), 2.48(t, 2H), 2.40-2.30(m,1H), 2.20-2.10(m, fluorobenzamide 1H), 1.72(q, 2H), 0.98(t, 3H) 66(S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.28(brs, 1H), 7.59(d, 1H),cyanophenylamino)-6- 7.48(brs, 1H), 7.40-7.20(m, 7H), 5.69(s, 1H),5.66(d, propylpyrimidin-4- 1H), 4.57(q, 1H), 3.58(s, 2H), 3.85-3.10(m,4H), 2.47(t, yl]pyrrolidin-3-yl}-2- 2H), 2.30-2.20(m, 1H), 1.90-1.80(m,1H), 1.70(q, 2H), phenylacetamide 0.97(t, 3H) 67 (S)-N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.31(brs, 1H), 7.57(d, 1H),cyanophenylamino)-6- 7.33(t, 1H), 7.30-7.20(m, 4H), 7.09(brs, 1H),7.02(t, 2H), propylpyrimidin-4- 5.72(s, 1H), 4.58(q, 1H), 3.53(s, 2H),3.90-3.20(m, 4H), yl]pyrrolidin-3-yl}-2-(4- 2.48(t, 2H), 2.30-2.20(m,1H), 1.90-1.85(m, 1H), 1.71(q, fluorophenyl)acetamide 1H), 0.97(t, 3H)68 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.29(brs, 1H), 7.90-7.80(m,cyanophenylamino)-6- 2H), 7.61(d, 1H), 7.33(t, 1H), 7.30-7.20(m, 3H),7.00(brs, propylpyrimidin-4- 1H), 6.94(t, 1H), 6.22(d, 1H), 5.74(s, 1H),4.62(q, 1H), yl]pyrrolidin-3-yl}-3- 4.26(t, 2H), 3.90-3.20(m, 4H),2.67(t, 2H), 2.49(t, 2H), phenoxypropanamide 2.35-2.25(m, 1H),1.80-1.60(m, 3H), 0.98(t, 3H) 69 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃)δ 8.02(s, 1H), 7.76(brs, 1H), cyanophenylamino)-6- 7.36(t, 1H),7.30-7.20(m, 1H), 6.89(brs, 1H), 5.70(s, 1H), propylpyrimidin-4-4.60(brs, 1H), 3.90-3.70(m, 3H), 3.65(t, 2H), 3.25-yl]pyrrolidin-3-yl}-3- 3.15(m, 3H), 2.63(t, 2H), 2.55-2.45(m, 3H),2.40-2.30(m, isobutoxypropanamide 1H), 1.75-1.65(m, 1H), 0.99(t, 3H),0.86(d, 6H) 70 (S)-2-(4-benzylpiperazin-1- ¹H-NMR(400 MHz, CDCl₃) δ8.40(brs, 1H), 7.65(brs, 1H), yl)-N-{1-[2-(3- 7.40-7.15(m, 8H), 5.75(s,1H), 5.30(s, 1H), 4.65-4.55(m, cyanophenylamino)-6- 1H), 3.90-3.30(m,4H), 3.02(s, 2H), 2.60-2.30(m, 11H), propylpyrimidin-4- 2.10-2.00(m,1H), 1.72(q, 2H), 0.99(t, 3H) yl]pyrrolidin-3-yl}acetamide

TABLE 1-8 Example Compound NMR Spectrum 71 (S)-N-{1-[2-(3- ¹H-NMR(400MHz, CDCl₃) δ 8.38(brs, 1H), 7.68(brs, 1H), cyanophenylamino)-6- 7.48(d,1H), 7.36(t, 1H), 7.24(d, 1H), 5.75(s, 1H), 4.60(q, propylpyrimidin-4-1H), 3.90-3.30(m, 4H), 3.01(s, 2H), 2.60-2.25(m, 7H),yl]pyrrolidin-3-yl}-2- 2.10-2.00(m, 1H), 1.71(q, 2H), 1.65-1.40(m, 6H),0.98(t, (piperidin-1-yl)acetamide 3H) 72 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz,CDCl₃) δ 8.35(brs, 1H), 8.03(s, 1H), cyanophenylamino)-6- 7.98(d, 2H),7.90-7.85(m, 1H), 7.80(brs, 1H), 7.58(t, 1H), propylpyrimidin-4-7.50-7.40(m, 3H), 7.33(t, 1H), 7.22(d, 1H), 7.12(brs, 1H),yl]pyrrolidin-3-yl}-4-oxo-4- 5.64(s, 1H), 4.63(brs, 1H), 3.90-3.20(m,6H), 2.80- phenylbutanamide 2.60(m, 2H), 2.49(t, 2H), 2.30-2.20(m, 1H),2.10-2.00(m, 1H), 1.67(q, 2H), 0.96(t, 3H) 73(S)-2-(4-aminophenyl)-N-{1- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(brs, 1H),7.60(brs, 1H), [2-(3-cyanophenylamino)-6- 7.34(t, 1H), 7.22(d, 1H),7.02(d, 2H), 6.66(d, 2H), 5.70(s, propylpyrimidin-4- 1H), 5.55(d, 1H),4.56(q, 1H), 3.90-3.50(m, 3H), 3.48(s, yl]pyrrolidin-3-yl}acetamide 2H),3.30-3.10(m, 1H), 2.48(d, 2H), 2.30-2.20(m, 1H), 2.00-1.90(m, 1H),1.71(q, 2H), 0.98(t, 3H) 74 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ8.33(brs, 1H), 7.61(brs, 1H), cyanophenylamino)-6- 7.34(t, 1H), 7.21(d,1H), 5.75(s, 1H), 5.63(brs, 1H), 4.65- propylpyrimidin-4- 4.55(m, 1H),3.90-3.20(m, 4H), 2.49(t, 2H), 2.30-2.10(m, yl]pyrrolidin-3-yl}-2- 3H),2.00-1.90(m, 1H), 1.90-1.45(m, 9H), 1.20-1.05(m, cyclopentylacetamide2H), 0.98(t, 3H) 75 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs,1H), 8.02(s, 1H), cyanophenylamino)-6- 7.78(d, 1H), 7.42(t, 1H),7.40-7.25(m, 2H), 6.70(brs, 1H), propylpyrimidin-4- 5.77(s, 1H),4.70-4.60(m, 1H), 3.91(s, 2H), 3.90-3.40(m, yl]pyrrolidin-3-yl}-2- 4H),3.42(s, 3H), 2.60(t, 2H), 2.40-2.30(m, 1H), 2.10- methoxyacetamide2.00(m, 1H), 1.72(q, 2H), 1.00(t, 3H) 76 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz,CDCl₃) δ 8.49(s, 1H), 8.40(brs, 1H), cyanophenylamino)-6- 8.05(brs, 1H),7.80-7.60(m, 2H), 7.40-7.15(m, 5H), propylpyrimidin-4- 5.73(s, 1H),4.60-4.50(m, 1H), 3.74(s, 2H), 3.90-3.20(m,yl]pyrrolidin-3-yl}-2-(pyridin- 4H), 2.55(t, 2H), 2.35-2.25(m, 1H),2.10-2.00(m, 1H), 2-yl)acetamide 1.70(t, 2H), 0.98(t, 3H) 77(S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.51(s, 2H), 8.32(brs, 1H),cyanophenylamino)-6- 7.71(t, 2H), 7.40-7.20(m, 4H), 6.45(brs, 1H),5.70(s, 1H), propylpyrimidin-4- 4.65-4.55(m, 1H), 3.57(s, 2H),3.90-3.30(m, 4H), 2.55(t, yl]pyrrolidin-3-yl}-2-(pyridin- 2H),2.30-2.20(m, 1H), 2.10-2.00(m, 1H), 1.69(q, 2H), 3-yl)acetamide 0.98(t,3H) 78 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.80(brs, 1H), 8.52(d,2H), cyanophenylamino)-6- 8.30(s, 1H), 7.70-7.65(m, 1H), 7.40-7.20(m,5H), propylpyrimidin-4- 6.63(brs, 1H), 5.68(s, 1H), 4.62(q, 1H), 3.56(s,2H), yl]pyrrolidin-3-yl}-2-(pyridin- 3.90-3.30(m, 4H), 2.53(t, 2H),2.35-2.25(m, 1H), 2.10- 4-yl)acetamide 2.00(m, 1H), 1.68(q, 2H), 0.97(t,3H) 79 (S,E)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(brs, 1H),7.60(brs, 1H), cyanophenylamino)-6- 7.40-7.00(m, 8H), 6.53(d, 1H),6.35-6.25(m, 1H), propylpyrimidin-4- 5.91(brs, 1H), 5.73(s, 1H),4.65-4.55(m, 1H), 3.90- yl]pyrrolidin-3-yl}-4- 3.25(m, 4H), 3.17(d, 2H),2.47(t, 2H), 2.35-2.25(m, 1H), phenylbut-3-enamide 2.00-1.80(m, 2H),1.71(q, 2H), 0.98(t, 3H) 80 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ8.30(brs, 1H), 7.61(brs, 1H), cyanophenylamino)-6- 7.40-7.10(m, 4H),7.00-6.85(m, 2H), 5.84(s, 1H), 5.69(s, propylpyrimidin-4- 1H),4.60-4.50(m, 1H), 3.79(s, 2H), 3.80-3.20(m, 4H), yl]pyrrolidin-3-yl}-2-2.49(t, 2H), 2.30-2.20(m, 1H), 2.00-1.85(m, 1H), 1.80-(thiophen-2-yl)acetamide 1.60(m, 2H), 1.00-0.90(m, 3H)

TABLE 1-9 Example Compound NMR Spectrum 81 (S)-N-{1-[2-(3- ¹H-NMR(400MHz, CDCl₃) δ 8.34(brs, 1H), 7.61(brs, 1H), cyanophenylamino)-6- 7.35(t,1H), 7.22(d, 1H), 5.75(s, 1H), 5.67(d, 1H), 4.60(q, propylpyrimidin-4-1H), 3.90-3.20(m, 4H), 2.49(t, 2H), 2.20-1.90(m, 2H), yl]pyrrolidin-3-1.17(d, 6H), 0.98(t, 3H) yljisobutyramide 82 (S)-N-{1-[2-(3- ¹H-NMR(400MHz, CDCl₃) δ 8.29(brs, 1H), 7.64(d, 1H), cyanophenylamino)-6- 7.34(t,1H), 7.22(d, 1H), 6.43(d, 1H), 5.73(s, 1H), 4.64(q, propylpyrimidin-4-1H), 4.00-3.30(m, 4H), 3.20-3.00(m, 2H), 2.51(t, 2H),yl]pyrrolidin-3-yl}-3,3,3- 2.40-2.30(m, 1H), 2.15-2.05(m, 1H), 1.71(q,2H), 0.99(t, trifluoropropanamide 3H) 83 3-[4-(2-oxopyrrolidin-1-yl)-6-¹H-NMR(400 MHz, CDCl₃) δ 8.26(s, 1H), 7.79(s, 1H), propylpyrimidin-2-7.60(d, 1H), 7.38(t, 1H), 7.27(d, 1H), 7.13(s, 1H), 4.11(t,ylamino]benzonitrile 2H), 2.75-2.55(m, 4H), 2.18(t, 2H), 1.77(q, 2H),0.99(t, 3H) 84 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H),7.57(d, 1H), (hexylamino)pyrrolidin-1-yl]- 7.33(t, 1H), 7.21(d, 1H),5.74(s, 1H), 3.90-3.20(m, 5H), 6-propylpyrimidin-2- 2.67(t, 2H), 2.48(t,2H), 2.25-2.15(m, 1H), 1.90-1.85(m, ylamino}benzonitrile 1H), 1.72(q,2H), 1.55-1.45(m, 2H), 1.40-1.20(m, 6H), 0.98(t, 3H), 0.95-0.85(m, 3H)85 (S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.57(d,1H), (propylamino)pyrrolidin-1- 7.34(t, 1H), 7.22(d, 1H), 5.75(s, 1H),4.00-3.20(m, 5H), yl]pyrimidin-2- 2.65(t, 2H), 2.48(t, 2H), 2.25-2.15(m,1H), 1.90-1.80(m, ylamino}benzonitrile 1H), 1.80-1.50(m, 6H),1.00-0.90(m, 6H) 86 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H),7.60(d, 1H), (cyclohexylmethylami- 7.50(brs, 1H), 7.33(t, 1H), 7.21(d,1H), 5.73(s, 1H), 4.00- no)pyrrolidin-1-yl]-6- 3.10(m, 5H), 2.50-2.40(m,4H), 2.25-2.15(m, 1H), 2.00- propylpyrimidin-2- 1.60(m, 9H),1.50-1.40(m, 1H), 1.30-1.10(m, 4H), 0.98(t, ylamino}benzonitrile 3H) 87(S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.41(s, 1H), 7.59(d, 1H),(benzylamino)pyrrolidin-1- 7.52(brs, 1H), 7.40-7.15(m, 7H), 5.72(s, 1H),3.87(s, yl]-6-propylpyrimidin-2- 2H), 3.80-3.10(m, 5H), 2.49(t, 2H),2.25-2.15(m, 1H), ylamino}benzonitrile 2.00-1.90(m, 1H), 1.80-1.60(m,2H), 0.98(t, 3H) 88 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H),7.56(d, 1H), (phenethylamino)pyrrolidin- 7.50-7.00(m, 7H), 5.73(s, 1H),3.95-3.75(m, 1H), 3.70- 1-yl]-6-propylpyrimidin-2- 3.30(m, 3H),3.25-3.10(m, 1H), 3.00-2.90(m, 2H), 2.84(t, ylamino}benzonitrile 2H),2.48(t, 2H), 2.25-2.15(m, 1H), 1.90-1.85(m, 1H), 1.72(q, 2H), 0.98(t,3H) 89 (S)-3-{4-[3-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.63(d,1H), phenylpropylamino)pyrrolidin- 7.39(t, 1H), 7.35-7.10(m, 6H),5.75(s, 1H), 4.00-3.20(m, 1-yl]-6-propylpyrimidin-2- 5H), 2.80-2.60(m,4H), 2.55(t, 2H), 2.30-2.00(m, 2H), ylamino}benzonitrile 2.00-1.90(m,2H), 1.80-1.70(m, 2H), 1.01(t, 3H) 90 (S)-3-{4-[3-(3- ¹H-NMR(400 MHz,CDCl₃) δ 8.43(s, 1H), 7.53(d, 1H), fluorobenzylamino)pyrrolidin-7.40-7.05(m, 6H), 6.95(t, 1H), 5.74(s, 1H), 3.87(s, 2H),1-yl]-6-propylpyrimidin-2- 3.80-3.10(m, 5H), 2.48(t, 2H), 2.25-2.15(m,1H), 2.00- ylamino}benzonitrile 1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H)

TABLE 1-10 Example Compound NMR Spectrum 91 (S)-3-{4-[3-(4- ¹H-NMR(400MHz, CDCl₃) δ 8.37(s, 1H), 7.52(d, 1H), hydroxybenzylamino)pyrrolidin-7.32(t, 1H), 7.25-7.15(m, 3H), 6.77(d, 2H), 5.73(s, 1H),1-yl]-6-propylpyrimidin- 3.78(s, 2H), 3.80-3.10(m, 5H), 2.48(t, 2H),1.25-1.15(m, 2-ylamino}benzonitrile 1H), 2.00-1.90(m, 1H), 1.71(q, 2H),0.97(t, 3H) 92 (S)-3-{4-[3-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H),7.59(d, 1H), ethylbenzylamino)pyrrolidin- 7.40-7.10(m, 6H), 5.72(s, 1H),3.84(s, 2H), 3.80-3.10(m, 1-yl]-6-propylpyrimidin-2- 5H), 2.63(q, 2H),2.48(t, 2H), 2.25-2.15(m, 1H), 2.00- ylamino}benzonitrile 1.90(m, 1H),1.72(q, 2H), 1.23(t, 3H), 0.98(t, 3H) 93 (S)-3-{4-[3- ¹H-NMR(400 MHz,CDCl₃) δ 8.38(s, 1H), 7.58(d, 1H), (isopentylamino)pyrrolidin- 7.33(t,1H), 7.20(d, 1H), 7.00(brs, 1H), 5.74(s, 1H), 3.90-1-yl]-6-propylpyrimidin-2- 3.00(m, 5H), 2.68(t, 2H), 2.48(t, 2H),2.25-2.15(m, 1H), ylamino}benzonitrile 1.90-1.80(m, 1H), 1.80-1.50(m,3H), 1.40(q, 2H), 0.98(t, 3H), 0.92(d, 6H) 94 (S)-3-{4-[3- ¹H-NMR(400MHz, CDCl₃) δ 8.39(s, 1H), 7.56(d, 1H), (pentylamino)pyrrolidin-1-7.34(t, 1H), 7.22(d, 1H), 7.00(brs, 1H), 5.75(s, 1H), 3.90-yl]-6-propylpyrimidin-2- 3.30(m, 5H), 2.67(t, 2H), 2.48(t, 2H),2.25-2.15(m, 1H), ylamino}benzonitrile 2.00-1.60(m, 3H), 1.52(t, 2H),1.40-1.20(m, 4H), 0.99(t, 3H), 0.92(t, 3H) 95 3-{4-[(3S)-3-(2-¹H-NMR(400 MHz, CDCl₃) δ 8.39(s, 1H), 7.58(d, 1H),methylbutylamino)pyrrolidin- 7.33(t, 1H), 7.20(d, 1H), 7.03(brs, 1H),5.74(s, 1H), 3.90- 1-yl]-6-propylpyrimidin-2- 3.10(m, 5H), 2.65-2.55(m,1H), 2.50-2.40(m, 3H), 2.25- ylamino}benzonitrile 2.15(m, 1H),1.90-1.80(m, 1H), 1.72(q, 2H), 1.50-1.35(m, 2H), 1.20-1.10(m, 1H),0.98(t, 3H), 0.95-0.85(m, 6H) 96 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.39(s, 1H), 7.55(d, 1H), (isobutylamino)pyrrolidin-1- 7.35(t, 1H),7.23(d, 1H), 5.75(s, 1H), 3.90-3.10(m, 5H), yl]-6-propylpyrimidin-2-2.55-2.45(m, 3H), 2.25-2.15(m, 1H), 1.90-1.85(m, 1H),ylamino}benzonitrile 1.80-1.60(m, 4H), 0.99(t, 3H), 0.94(d, 6H) 97(S)-3-{4-[3-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.56(d, 1H),methoxybenzylamino)pyrrolidin- 7.33(t, 1H), 7.26(t, 2H), 7.21(d, 1H),6.87(d, 2H), 5.73(s, 1-yl]-6-propylpyrimidin- 1H), 3.81(s, 2H), 3.80(s,3H), 3.80-3.10(m, 5H), 2.48(t, 2-ylamino}benzonitrile 2H), 2.25-2.15(m,1H), 2.00-1.90(m, 1H), 1.80-1.60(m, 2H), 0.98(t, 3H) 98 (S)-3-{4-[3-(4-¹H-NMR(400 MHz, CDCl₃) δ 8.44(s, 1H), 7.54(d, 1H),fluorobenzylamino)pyrrolidin- 7.40-7.30(m, 3H), 7.21(d, 1H), 7.01(d,2H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2- 3.84(s, 2H), 3.80-3.10(m,5H), 2.48(t, 2H), 2.25-2.15(m, ylamino}benzonitrile 1H), 2.00-1.90(m,1H), 1.72(q, 2H), 0.98(t, 3H) 99 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.39(s, 1H), 7.56(d, 1H), (cyclopropylmethylamino)pyrrol- 7.35(t, 1H),7.24(d, 1H), 5.75(s, 1H), 3.90-3.20(m, 5H),idin-1-yl]-6-propylpyrimidin- 2.56(d, 2H), 2.49(t, 2H), 2.25-2.15(m,1H), 2.00-1.90(m, 2-ylamino}benzonitrile 1H), 1.80-1.65(m, 2H),1.00-0.90(m, 4H), 0.53(d, 2H), 0.17(d, 2H) 100 (S)-3-(4-{3- ¹H-NMR(400MHz, CDCl₃) δ 8.39(s, 1H), 7.58(d, 1H), [bis(cyclopropylmethyl)ami-7.32(t, 1H), 7.20(d, 1H), 7.08(brs, 1H), 5.73(s, 1H), 4.00-no]pyrrolidin-1-yl}-6- 3.10(m, 5H), 2.70-2.55(m, 4H), 2.48(t, 2H),2.25-2.15(m, propylpyrimidin-2- 1H), 2.00-1.90(m, 1H), 1.80-1.65(m, 2H),1.00-0.90(m, ylamino)benzonitrile 5H), 0.55(d, 4H), 0.18(d, 4H)

TABLE 1-11 Example Compound NMR Spectrum 101 (S)-3-{4-propyl-6-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.52(s, 1H), 7.70-7.60(m, (pyridin-2- 2H),7.51(brs, 1H), 7.33(t, 1H), 7.21(d, 1H), 7.15(t, 2H),ylmethylamino)pyrrolidin-1- 5.68(s, 1H), 3.95(s, 2H), 4.00-3.20(m, 5H),2.48(t, 2H), yl]pyrimidin-2- 2.50-2.20(m, 2H), 1.71(q, 2H), 0.98(t, 3H)ylamino}benzonitrile 102 (S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.65-8.45(m, 3H), 7.70(t, (pyridin-3- 1H), 7.55(d, 1H), 7.40-7.15(m,3H), 5.73(s, 1H), 3.89(s, ylmethylamino)pyrrolidin-1- 2H), 3.90-3.20(m,5H), 2.48(t, 2H), 2.25-2.15(m, 1H), yl]pyrimidin-2- 2.00-1.90(m, 1H),1.80-1.60(m, 2H), 0.98(t, 3H) ylamino}benzonitrile 103(S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.60-8.40(m, 3H),8.10(brs, (pyridin-4- 1H), 7.60-7.50(m, 1H), 7.40-7.15(m, 4H), 5.73(s,1H), ylmethylamino)pyrrolidin-1- 3.90(s, 2H), 3.90-3.10(m, 5H), 2.48(t,2H), 2.25-2.15(m, yl]pyrimidin-2- 1H), 2.00-1.90(m, 1H), 1.72(q, 2H),0.99(t, 3H) ylamino}benzonitrile 104 (S)-3-{4-[3-(2- ¹H-NMR(400 MHz,CDCl₃) δ 8.41(s, 1H), 7.58(d, 1H), ethylbutylamino)pyrrolidin- 7.33(t,1H), 7.21(d, 1H), 5.74(s, 1H), 3.90-3.00(m, 5H),1-yl]-6-propylpyrimidin-2- 2.48(t, 2H), 2.40(brs, 2H), 2.25-2.15(m, 1H),1.88(brs, ylamino}benzonitrile 1H), 1.72(q, 2H), 0.98(t, 3H), 0.92(s,9H) 105 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.41(s, 1H), 7.58(d, 1H),(neopentylamino)pyrrolidin- 7.33(t, 1H), 7.21(d, 1H), 5.74(s, 1H),3.90-3.00(m, 5H), 1-yl]-6-propylpyrimidin-2- 2.48(t, 2H), 2.40(brs, 2H),2.25-2.15(m, 1H), 1.88(brs, ylamino}benzonitrile 1H), 1.72(q, 2H),0.98(t, 3H), 0.92(s, 9H) 106 (S)-3-{4-[3-(2- ¹H-NMR(400 MHz, CDCl₃) δ8.39(s, 1H), 7.60(d, 1H), fluorobenzylamino)pyrrolidin- 7.50-7.20(m,4H), 7.12(t, 1H), 7.05(t, 1H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2-3.92(s, 2H), 3.90-3.10(m, 5H), 2.48(t, 2H), 2.25-2.15(m,ylamino}benzonitrile 1H), 2.00-1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H) 107(S)-3-(4-propyl-6-{3-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.45(s, 1H), 7.64(s,1H), (trifluoromethyl)benzyl- 7.60-7.40(m, 4H), 7.33(t, 1H), 7.21(d,1H), 5.73(s, 1H), amino]pyrrolidin-1-yl}pyrimidin- 3.94(s, 2H),3.90-3.10(m, 5H), 2.49(t, 2H), 2.25-2.15(m, 2-ylamino)benzonitrile 1H),2.00-1.90(m, 1H), 1.72(q, 2H), 0.98(t, 3H) 108 (S)-3-(4-propyl-6-{3-[4-¹H-NMR(400 MHz, CDCl₃) δ 8.48(s, 1H), 7.70-7.40(m,(trifluoromethyl)benzyl- 5H), 7.33(t, 1H), 7.21(d, 1H), 5.72(s, 1H),3.94(s, 2H), amino]pyrrolidin-1-yl}pyrimidin- 3.90-3.10(m, 5H), 2.48(t,2H), 2.25-2.15(m, 1H), 2.00- 2-ylamino)benzonitrile 1.90(m, 1H), 1.72(q,2H), 0.98(t, 3H) 109 (S)-4-({1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.39(s,1H), 7.53(d, 1H), cyanophenylamino)-6- 7.33(t, 1H), 7.25-7.15(m, 3H),6.78(d, 2H), 5.74(s, 1H), propylpyrimidin-4- 3.79(s, 2H), 3.70-3.10(m,5H), 2.49(s, 2H), 2.25-2.15(m, yl]pyrrolidin-3- 2H), 1.92(brs, 3H),1.72(q, 2H), 0.98(t, 3H) ylamino}methyl)phenylacetate 110(S)-3-(4-{3-[4- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(s, 1H), 7.57(dd, 1H),(dimethylamino)benzyl- 7.35(t, 1H), 7.30-7.15(m, 3H), 6.71(d, 2H),5.74(s, 1H), amino]pyrrolidin-1-yl}-6- 3.78(s, 2H), 3.80-3.30(m, 5H),2.93(s, 6H), 2.50(t, 2H), propylpyrimidin-2- 2.25-2.15(m, 1H),2.00-1.90(m, 1H), 1.73(q, 2H), 0.99(t, ylamino)benzonitrile 3H)

TABLE 1-12 Example Compound NMR Spectrum 111 (S)-3-(4-{3-[(1H-pyrrol-2-¹H-NMR(400 MHz, CDCl₃) δ 8.41(brs, 1H), 7.52(brs, 1H),yl)methylamino]pyrrolidin-1- 7.34(t, 1H), 7.23(d, 1H), 6.74(s, 1H),6.14(d, 1H), 6.08(s, yl}-6-propylpyrimidin-2- 1H), 5.71(s, 1H), 3.90(s,2H), 3.80-3.10(m, 5H), 2.49(t, ylamino)benzonitrile 2H), 2.25-2.15(m,1H), 1.90-1.85(m, 1H), 1.71(q, 2H), 0.99(t, 3H) 112(S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.41(s, 1H), 7.59(d, 1H),(thiophen-2- 7.55(brs, 1H), 7.33(t, 1H), 7.30-7.20(m, 2H), 7.00-ylmethylamino)pyrrolidin-1- 6.90(m, 2H), 5.73(s, 1H), 4.08(s, 2H),3.90-3.10(m, 5H), yl]pyrimidin-2- 2.48(t, 2H), 2.25-2.15(m, 1H),2.00-1.90(m, 1H), 1.72(q, ylamino}benzonitrile 2H), 0.98(t, 3H) 113(S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.44(s, 1H), 7.57(d, 1H),(thiophen-3- 7.50(brs, 1H), 7.40-7.25(m, 2H), 7.25-7.15(m, 2H),ylmethylamino)pyrrolidin-1- 7.07(d, 1H), 5.73(s, 1H), 3.90(s, 2H),3.90-3.10(m, 5H), yl]pyrimidin-2- 2.48(t, 2H), 2.25-2.15(m, 1H),2.00-1.90(m, 1H), 1.72(q, ylamino}benzonitrile 2H), 0.98(t, 3H) 114(S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.37(brs, 1H), 7.60(brs, 1H),(dibutylamino)pyrrolidin-1- 7.32(t, 1H), 7.20(d, 1H), 7.13(brs, 1H),5.74(s, 1H), yl]-6-propylpyrimidin-2- 3.90(brs, 1H), 3.60-3.10(m, 4H),2.75-2.40(m, 6H), 2.20- ylamino}benzonitrile 2.10(m, 1H), 2.00-1.90(m,1H), 1.73(q, 2H), 1.50-1.20(m, 8H), 1.00-0.90(m, 9H) 115(S)-3-(4-{3-bis[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.42(brs, 1H), 7.57(d, 1H),(methylthio)propyl]amino- 7.33(t, 1H), 7.20(d, 1H), 5.74(s, 1H),3.90(brs, 1H), 3.65- pyrrolidin-1-yl}-6- 3.10(m, 4H), 2.70-2.60(m, 4H),2.54(t, 4H), 2.49(t, 2H), propylpyrimidin-2- 2.25-2.15(m, 1H), 2.11(s,6H), 2.00-1.90(m, 1H), 1.80- ylamino)benzonitrile 1.65(m, 6H), 0.98(t,3H) 116 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.33(s, 1H), 7.58(d, 1H),(butylamino)pyrrolidin-1-yl]- 7.34(t, 1H), 7.22(d, 1H), 5.75(s, 1H),3.90-3.10(m, 5H), 6-propylpyrimidin-2- 2.73(t, 2H), 2.49(t, 2H),2.30-2.20(m, 1H), 2.10-1.95(m, ylamino}benzonitrile 1H), 1.72(q, 2H),1.55-1.45(m, 2H), 1.45-1.30(m, 2H), 1.00-0.85(m, 6H) 117 (S)-3-(4-{3-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.57(d, 1H), (methylthio)propyl-7.37(t, 1H), 7.30-7.20(m, 1H), 5.77(s, 1H), 3.90-3.10(m,amino]pyrrolidin-1-yl}- 5H), 2.90-2.70(m, 2H), 2.58(t, 2H), 2.51(t, 2H),2.30- 6-propylpyrimidin-2- 2.20(m, 1H), 2.11(s, 3H), 2.00-1.90(m, 1H),1.90-1.70(m, ylamino)benzonitrile 4H), 1.00(t, 3H) 118(S)-3-{4-propyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.45(d, 1H), 7.77(t, 1H),(propylamino)pyrrolidin-1- 7.41(t, 1H), 7.25(d, 1H), 5.98(s, 1H),4.10-3.90(m, 2H), yl]pyrimidin-2- 3.85-3.50(m, 3H), 3.10-3.00(m, 2H),2.60-2.40(m, 3H), ylamino}benzonitrile 2.30-2.20(m, 1H), 1.80-1.65(m,3H), 1.50-1.40(m, 1H), dihydrochloride 1.10-0.90(m, 6H) 119 (S)-3-{4-[3-¹H-NMR(400 MHz, CD₃OD) δ 8.15(d, 1H), 7.90-7.80(m, (cyclopropylmethyl-1H), 7.60-7.45(m, 2H), 6.35(d, 1H), 4.25-3.65(m, 5H),amino)pyrrolidin-1-yl]- 3.15-2.90(m, 2H), 2.70-2.50(m, 3H), 2.50-2.25(m,1H), 6-propylpyrimidin-2- 1.90-1.70(m, 2H), 1.20-1.10(m, 1H),1.10-0.95(m, 3H), ylamino}benzonitrile 0.80-0.65(m, 2H), 0.50-0.40(m,2H) dihydrochloride 120 (S)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.16(brs,1H), 7.83(d, 1H), (methylamino)pyrrolidin-1- 7.61-7.53(m, 2H), 6.34(s,1H), 4.12-3.79(m, 5H), 2.81(s, yl]-6-propylpyrimidin-2- 3H), 2.69(dd,2H), 2.58(brs, 1H), 2.38(brs, 1H), 1.85- ylamino}benzonitrile 1.76(m,2H), 1.06(dd, 3H) dihydrochloride

TABLE 1-13 Example Compound NMR Spectrum 121 (S)-N-{4-[3- ¹H-NMR(400MHz, CD₃OD) δ 8.03(s, 1H), 7.41(d, 1H), (methylamino)pyrrolidin-1-7.12(d, 1H), 7.04(d, 1H), 6.35(d, 1H), 5.82(s, 1H), 3.90-yl]-6-propylpyrimidin-2-yl}- 3.30(m, 5H), 2.50-2.40(m, 5H), 2.30-2.20(m,1H), 2.00- 1H-indol-6-amine 1.90(m, 1H), 1.73(q, 2H), 0.99(t, 3H) 122(S)-N-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.66(s, 1H), 7.57(d, 1H),(methylamino)pyrrolidin-1- 7.27(d, 1H), 7.04(d, 1H), 6.46(d, 1H),6.19(s, 1H), 4.10- yl]-6-propylpyrimidin-2-yl}- 3.60(m, 5H), 2.78(s,3H), 2.62(t, 2H), 2.55(brs, 1H), 1H-indol-6-amine 2.31(brs, 1H), 1.75(q,2H), 1.04(t, 3H) hydrochloride 123 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CD₃OD)δ 7.97(d, 1H), 7.65-7.55(m, (methylamino)pyrrolidin-1- 1H), 7.21(t, 1H),6.30(d, 1H), 4.15-3.75(m, 5H), 2.79(d, yl]-6-propylpyrimidin-2-yl}-3-3H), 2.69(t, 2H), 2.65-2.50(m, 1H), 2.50-2.25(m, 1H),(trifluoromethyl)benzene- 1.90-1.70(m, 2H), 1.07(t, 3H) 1,4-diaminedihydrochloride 124 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.45(s,1H), 7.98(brs, 1H), cyanophenylamino)-6- 7.60-7.50(m, 1H), 7.34(t, 1H),7.22(d, 1H), 6.27(brs, 1H), propylpyrimidin-4- 5.53(s, 1H), 4.24(brs,1H), 3.80-3.20(m, 5H), 2.50- yl]pyrrolidin-3- 2.35(m, 2H), 2.30-2.00(m,2H), 1.70-1.50(m, 2H), 1.46(d, yl}isopropane-2- 6H), 0.95(t, 3H)sulfonamide 125 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.43(s, 1H),7.61(d, 1H), cyanophenylamino)-6- 7.35(t, 1H), 7.24(d, 1H), 5.66(s, 1H),4.24(brs, 1H), 3.90- propylpyrimidin-4- 3.30(m, 5H), 3.08(s, 3H),2.50-2.20(m, 4H), 1.67(q, 2H), yl]pyrrolidin-3- 0.98(t, 3H)yl}methanesulfonamide 126 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ8.35(s, 1H), 8.00-7.90(m, cyanophenylamino)-6- 2H), 7.54(d, 1H), 7.33(t,1H), 7.30-7.15(m, 3H), 5.54(s, propylpyrimidin-4- 1H), 4.10(brs, 1H),3.70-3.30(m, 4H), 2.50-2.25(m, 2H), yl]pyrrolidin-3-yl}-4- 2.20-2.00(m,2H), 1.58(q, 2H), 0.91(t, 3H) fluorobenzenesulfonamide 1273-{4-[(3S)-3-(sec- ¹H-NMR(400 MHz, CD₃OD) δ 8.36(s, 1H), 7.58(d, 1H),butylamino)pyrrolidin-1-yl]- 7.33(dd, 1H), 7.20(d, 1H), 7.10(s, 1H),5.74(s, 1H), 4.10- 6-propylpyrimidin-2- 3.10(m, 5H), 2.71-2.67(m, 1H),2.48(dd, 2H), 2.26- ylamino}benzonitrile 2.21(m, 1H), 1.77-1.67(m, 3H),1.52-1.46(m, 1H), 1.39- 1.34(m, 1H), 1.10-1.07(m, 3H), 0.98(t, 3H),0.94-0.90(m, 3H) 128 (S)-3-{4-[3-(pentan-3- ¹H-NMR(400 MHz, CDCl₃) δ10.02(brs, 1H), 8.42(s, 1H), ylamino)pyrrolidin-1-yl]-6- 7.70(d, 1H),7.35(dd, 1H), 7.24(d, 1H), 5.71(s, 1H), 3.88- propylpyrimidin-2- 3.12(m,5H), 2.53-2.45(m, 3H), 2.26-2.18(m, 1H), 2.10(s, ylamino}benzonitrile3H), 1.94-1.88(m, 1H), 1.76-1.67(m, 2H), 1.52-1.44(m, 4H), 0.98(t, 3H),0.95-0.90(m, 6H) 129 (S)-3-{4-[3-(2,6- ¹H-NMR(400 MHz, CDCl₃) δ8.35(brs, 1H), 7.65(brs, 1H), dimethylheptan-4- 7.33(dd, 1H),7.22-7.20(m, 2H), 5.74(s, 1H), 3.88- ylamino)pyrrolidin-1-yl]-6- 3.12(m,5H), 2.83-2.82(m, 1H), 2.48(dd, 2H), 2.24- propylpyrimidin-2- 2.21(m,1H), 1.84-1.62(m, 7H), 1.39-1.36(m, 1H), 1.26- ylamino}benzonitrile1.22(m, 1H), 1.14-1.02(m, 3H), 0.98(t, 3H), 0.88-0.81(m, 9H)

TABLE 1-14 Example Compound NMR Spectrum 130 (S)-3-{4-[3-(4,4-¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, 1H), 7.62(brs, 2H), dimethylpentan-2-7.33(dd, 1H), 7.21(d, 1H), 5.73(s, 1H), 3.84-3.07(m, 5H),ylamino)pyrrolidin-1-yl]-6- 2.85-2.81(m, 1H), 2.49(dd, 2H), 2.27-2.20(m,1H), 1.77- propylpyrimidin-2- 1.70(m, 3H), 1.37-1.30(m, 2H), 1.12(d,3H), 1.04-0.81(m, ylamino}benzonitrile 12H) 131(S)-3-{4-[3-(3-hydroxy-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.49-8.35(m, 1H),7.68(brs, methylbutan-2- 1H), 7.37-7.33(m, 1H), 7.25-7.23(m, 1H),5.71(s, 1H), ylamino)pyrrolidin-1-yl]-6- 3.92-3.22(m, 5H), 2.54-2.49(m,3H), 2.29-2.25(m, 1H), propylpyrimidin-2- 2.12-2.06(m, 1H), 1.75-1.66(m,2H), 1.21(d, 3H), 1.16- ylamino}benzonitrile 1.13(m, 3H), 1.05(s, 3H),1.00(t, 3H) 132 (S)-3-{4-[3-(heptan-4- ¹H-NMR(400 MHz, CDCl₃) δ8.36(brs, 1H), 7.62(brs, 1H), ylamino)pyrrolidin-1-yl]-6- 7.47(brs, 1H),7.33(m, 1H), 7.20(d, 1H), 5.71(s, 1H), propylpyrimidin-2- 3.82-3.06(m,5H), 2.58-2.56(m, 1H), 2.49(dd, 2H), 2.24- ylamino}benzonitrile 2.16(m,1H), 1.94-1.90(m, 1H), 1.77-1.68(m, 2H), 1.43- 1.36(m, 8H), 1.00(t, 3H),0.95-0.85(m, 6H) 133 (S)-3-{4-[3-(n-hexan-2- ¹H-NMR(400 MHz, CDCl₃) δ9.35(brs, 1H), 8.42(brs, 1H), ylamino)pyrrolidin-1-yl]-6- 7.34(dd, 1H),7.23(d, 1H), 5.71(s, 1H), 3.85-3.10(m, 5H), propylpyrimidin-2-2.75-2.71(m, 1H), 2.50(dd, 2H), 2.26-2.22(m, 1H), 1.94-ylamino}benzonitrile 1.87(m, 1H), 1.74-1.69(m, 2H), 1.45-1.31(m, 6H),1.11- 0.88(m, 9H) 134 (S)-3-{4-[3-(5-methylhexan- ¹H-NMR(400 MHz, CDCl₃)δ 8.34(brs, 2H), 7.63(d, 1H), 2-ylamino)pyrrolidin-1-yl]-6- 7.33(dd,1H), 7.21(d, 1H), 5.72(s, 1H), 3.85-3.10(m, 5H), propylpyrimidin-2-2.74-2.70(m, 1H), 2.49(dd, 2H), 2.26-2.21(m, 1H), 1.94-ylamino}benzonitrile 1.87(m, 1H), 1.74-1.69(m, 2H), 1.54-1.17(m, 5H),1.10- 1.08(m, 3H), 0.98(t, 3H), 0.90-0.86(m, 6H) 135 (S)-3-{4-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.45(s, 1H), 7.72(d, 1H),(cyclohexylamino)pyrrolidin- 7.35(dd, 1H), 7.25(d, 1H), 5.69(s, 1H),3.95-3.15(m, 5H), 1-yl]-6-propylpyrimidin-2- 2.54-2.52(m, 3H),2.27-2.23(m, 2H), 1.93(brs, 3H), 1.78- ylamino}benzonitrile 1.63(m, 5H),1.32-1.15(m, 5H), 0.98(t, 3H) 136 (S)-tert-butyl 2-{1-[2-(3- ¹H-NMR(400MHz, CDCl₃) δ 8.42(s, 1H), 7.58(d, 1H), cyanophenylamino)-6- 7.33(dd,1H), 7.20(d, 1H), 5.73(s, 1H), 4.97(brs, 1H), propylpyrimidin-4-3.72-3.25(m, 9H), 2.81(brs, 1H), 2.48(dd, 2H), 2.23- yl]pyrrolidin-3-2.18(m, 1H), 1.88(brs, 1H), 1.76-1.71(m, 2H), 1.44(s,ylamino}ethylcarbamate 9H), 0.98(t, 3H) 137 (S)-3-{4-[3-(1- ¹H-NMR(400MHz, CDCl₃) δ 8.39(s, 1H), 7.57(d, 1H), benzylpiperidin-4- 7.35-7.19(m,6H), 7.09(brs, 1H), 5.73(s, 1H), 3.76- ylamino)pyrrolidin-1-yl]-6-3.58(m, 3H), 3.51(s, 2H), 3.51-3.05(m, 2H), 2.87(d, 2H),propylpyrimidin-2- 2.61-2.54(m, 1H), 2.47(dd, 2H), 2.23-2.19(m, 1H),ylamino}benzonitrile 2.05(dd, 2H), 1.89-1.85(m, 3H), 1.76-1.67(m, 2H),1.46- 1.37(m, 2H), 0.97(t, 3H) 138 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.38(s, 1H), 7.59(d, 1H), (isopropylamino)pyrrolidin- 7.32(dd, 1H),7.20(d, 1H), 7.11(brs, 1H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2-4.10-2.99(m, 5H), 2.99-2.93(m, 1H), 2.48(dd, 2H), 2.28-ylamino}benzonitrile 2.21(m, 1H), 1.84(brs, 1H), 1.77-1.67(m, 2H),1.11(dd, 6H), 0.97(t, 3H) 139 (S)-3-{4-[3-(1- ¹H-NMR(400 MHz, CDCl₃) δ8.54(brs, 1H), 7.47-7.40(m, benzoylpiperidin-4- 6H), 7.33(dd, 1H),7.21(d, 1H), 5.73(s, 1H), 4.63(brs, ylamino)pyrrolidin-1-yl]-6- 1H),4.23-2.90(m, 9H), 2.48(dd, 2H), 2.27-2.23(m, 1H), propylpyrimidin-2-2.11-1.69(m, 7H), 0.98(t, 3H) ylamino}benzonitrile

TABLE 1-15 Example Compound NMR Spectrum 140 (S)-3-{4-[3-(1- ¹H-NMR(400MHz, CDCl₃) δ 8.50-8.37(m, 1H), 7.60- acetylpiperidin-4- 7.49(m, 1H),7.32(dd, 1H), 7.20(d, 1H), 7.14(brs, 1H), ylamino)pyrrolidin-1-yl]-6-5.74(s, 1H), 4.51(d, 1H), 3.89-3.38(m, 6H), 3.15(dd, 1H),propylpyrimidin-2- 2.84(brs, 1H), 2.76(dd, 1H), 2.48(dd, 2H),2.26-2.20(m, ylamino}benzonitrile 1H), 2.10(s, 3H), 1.97-1.89(m, 3H),1.76-1.67(m, 2H), 1.30-1.25(m, 2H), 0.98(t, 3H) 141 (S)-3-{4-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.38(brs, 1H), 7.56(brs, 1H),(cyclooctylamino)pyrrolidin- 7.33(dd, 1H), 7.20(d, 1H), 7.16(brs, 1H),5.73(s, 1H), 1-yl]-6-propylpyrimidin-2- 3.89-3.38(m, 5H), 2.79(brs, 1H),2.53-2.45(m, 4H), 2.23- ylamino}benzonitrile 2.09(m, 3H), 2.01-1.50(m,14H), 0.98(t, 3H) 142 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.37(brs,1H), 7.59(d, 1H), (cyclobutylamino)pyrrolidin- 7.33(dd, 1H), 7.20(d,1H), 7.00(brs, 1H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2- 3.83-3.32(m,6H), 2.47(dd, 2H), 2.29-2.15(m, 3H), ylamino}benzonitrile 1.85(brs, 1H),1.79-1.64(m, 6H), 0.98(t, 3H) 143 (S)-3-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ8.37(brs, 1H), 7.58(d, 1H), (cyclopentylamino)pyrrolidin- 7.32(dd, 1H),7.19(d, 1H), 7.18(brs, 1H), 5.73(s, 1H), 1-yl]-6-propylpyrimidin-2-3.99-3.14(m, 6H), 2.47(dd, 2H), 2.28-2.20(m, 1H), 1.93-ylamino}benzonitrile 1.88(m, 3H), 1.76-1.67(m, 4H), 1.64-1.51(m, 2H),1.38- 1.24(dd, 2H), 0.97(t, 3H) 144 (S)-tert-butyl 3-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, 1H), 7.59(d, 1H),cyanophenylamino)-6- 7.32(dd, 1H), 7.21(brs, 1H), 7.20(d, 1H), 5.76(brs,1H), propylpyrimidin-4- 4.65(d, 4H), 3.97-3.40(m, 6H), 2.48(dd, 2H),2.26- yl]pyrrolidin-3- 2.05(m, 2H), 1.74-1.69(m, 2H), 1.49(s, 9H),0.97(t, 3H) ylamino}azetidine-1- carboxylate 145 (S)-3-(4-{3-[2-¹H-NMR(400 MHz, CDCl₃) δ 8.44(s, 1H), 7.70(d, 1H),(benzyloxy)ethylamino]pyrrolidin- 7.37-7.23(m, 7H), 5.69(s, 1H), 4.53(s,2H), 3.85-3.19(m, 1-yl}-6-propylpyrimidin-2- 7H), 2.89(brs, 2H),2.52(dd, 2H), 2.25-2.17(m, 1H), ylamino)benzonitrile 2.10(s, 3H),1.94(brs, 1H), 1.76-1.67(m, 2H), 0.99(t, 3H) 146 (S)-N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.61(s, 1H), cyanophenylamino)-6-7.54(s, 1H), 7.33(t, 1H), 7.19(d, 1H), 5.81(m, 1H), propylpyrimidin-4-5.80(s, 1H), 4.62(m, 1H), 3.78-3.01(m, 4H), 2.48(t, 2H),yl]pyrrolidin-3- 2.32(m, 1H), 2.23(m, 2H), 2.01(m, 1H), 1.72(m, 2H),yl}propionamide 1.17(t, 3H), 0.98(t, 3H) 147 (S)-N-{1-[2-(3- ¹H-NMR(400MHz, CDCl₃) δ 8.45(s, 1H), 7.71(s, 1H), cyanophenylamino)-6- 7.35(t,1H), 7.23(d, 1H), 5.77(s, 1H), 5.71(s, 1H), propylpyrimidin-4- 4.59(m,1H), 3.81-3.22(m, 4H), 2.47(t, 2H), 2.34(m, 1H),yl]pyrrolidin-3-yl}pivalamide 2.01(m, 1H), 1.67(q, 2H), 1.21(s, 9H),0.98(t, 3H) 148 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.25(s, 1H),7.53(s, 1H), cyanophenylamino)-6- 7.26(t, 1H), 7.13(d, 1H), 7.09(brs,1H), 5.69(s, 1H), propylpyrimidin-4- 4.53(m, 1H), 3.75-3.21(m, 4H),2.43(t, 2H), 2.25(m, 1H), yl]pyrrolidin-3-yl}-2,2- 1.86(m, 1H), 1.66(m,2H), 1.47(m, 2H), 1.09(s, 6H), dimethylbutanamide 0.91(t, 3H), 0.75(t,3H)

TABLE 1-16 Example Compound NMR Spectrum 149 (S,E)-N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.34(s, 1H), 7.61(s, 1H), cyanophenylamino)-6-7.34(t, 1H), 7.22(d, 1H), 7.06(s, 1H), 6.45(m, 1H), propylpyrimidin-4-5.86(m, 1H), 5.76(s, 1H), 4.66(m, 1H), 3.81-3.37(m, 4H),yl]pyrrolidin-3-yl}-2- 2.48(t, 2H), 2.34(m, 1H), 2.05(m, 1H), 1.85(s,3H), methylbut-2-enamide 1.71(m, 5H), 0.98(t, 3H) 150 (S)-N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.60(s, 1H), cyanophenylamino)-6-7.34(t, 1H), 7.20(d, 1H), 7.06(s, 1H), 5.75(s, 1H), propylpyrimidin-4-5.67(m, 1H), 4.60(m, 1H), 3.77-3.34(m, 4H), 2.50(t, 2H),yl]pyrrolidin-3- 2.31(m, 1H), 2.17(t, 2H), 2.02(m, 1H), 1.76-1.62(m,4H), yl}hexanamide 1.31(m, 6H), 0.98(t, 3H), 0.89(t, 3H) 151(S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 7.59(s, 1H),cyanophenylamino)-6- 7.35(t, 1H), 7.27-7.12(m, 7H), 5.70(s, 1H), 5.57(m,1H), propylpyrimidin-4- 4.55(m, 1H), 3.69(m, 4H), 2.97(t, 2H), 2.49(m,4H), yl]pyrrolidin-3-yl}-3- 2.22(m, 1H), 1.73(m, 1H), 1.69(m, 2H),0.98(t, 3H) phenylpropanamide 152 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃)δ 8.30(s, 1H), 8.26(s, 1H), cyanophenylamino)-6- 7.52(m, 2H),7.39-7.31(m, 2H), 7.22-7.16(m, 2H), propylpyrimidin-4- 7.09(m, 1H),5.80(m, 1H), 5.65(s, 1H), 4.58(m, 1H), yl]pyrrolidin-3-yl}-2-(1H-3.76(s, 2H), 3.34-3.20(m, 4H), 2.46(t, 2H), 2.25(m, 1H),indol-3-yl)acetamide 1.71(m, 3H), 0.97(t, 3H) 153 (S)-N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.37(s, 1H), 7.58(d, 1H), cyanophenylamino)-6-7.32(t, 1H), 7.20(d, 2H), 6.97(m, 1H), 5.75(s, 1H), propylpyrimidin-4-4.59(m, 1H), 3.83-3.34(m, 4H), 2.51(t, 2H), 2.31(m, 1H),yl]pyrrolidin-3-yl}-2-hydroxy- 2.03(m, 1H), 1.71(m, 2H), 1.47(s, 6H),0.98(t, 3H) 2-methylpropanamide 154 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz,CDCl₃) δ 8.28(s, 1H), 7.62(s, 1H), cyanophenylamino)-6- 7.48(s, 1H),7.32(t, 1H), 7.18(d, 1H), 7.08(d, 1H), 6.80(d, propylpyrimidin-4- 1H),5.70(s, 1H), 5.65(m, 1H), 4.56(m, 1H), 3.73(s, 3H),yl]pyrrolidin-3-yl}-3-(4- 3.69-3.00(m, 4H), 2.90(t, 2H), 2.46(m, 4H),2.21(m, 1H), methoxyphenyl)propanamide 1.90(m, 1H), 1.69(m, 2H), 0.98(t,3H) 155 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.01(s, 1H), 7.50(s,1H), cyanophenylamino)-6- 7.37(t, 1H), 7.20(d, 1H), 7.04(d, 2H), 6.78(d,2H), 5.69(s, propylpyrimidin-4- 1H), 5.47(m, 1H), 4.55(m, 1H),3.75-3.24(m, 4H), yl]pyrrolidin-3-yl}-3-(4- 2.89(m, 2H), 2.49(m, 4H),1.68(m, 2H), 0.96(t, 3H) hydroxyphenyl)propanamide 156 (S)-N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H), 7.78(s, 1H), cyanophenylamino)-6-7.65(s, 1H), 7.33(t, 1H), 7.19(d, 1H), 5.59(s, 1H), propylpyrimidin-4-4.61(m, 1H), 3.65-3.00(m, 4H), 2.89(m, 2H), 2.48(m,yl]pyrrolidin-3-yl}-4- 4H), 2.22(s, 3H + 1H), 2.06(m, 1H), 1.64(m, 2H),0.95(t, oxopentanamide 3H) 157 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ8.36(s, 1H), 7.59(d, 1H), cyanophenylamino)-6- 7.47(s, 1H), 7.33(t, 1H),7.19(d, 1H), 6.83(d, 1H), 5.73(s, propylpyrimidin-4- 1H), 4.65(m, 1H),4.14(s, 2H), 3.81-3.43(m, 4H), 2.48(t, yl]pyrrolidin-3-yl}-2- 2H),2.33(m, 1H), 2.05(m, 1H), 1.70(m, 2H), 0.98(t, 3H) hydroxyacetamide

TABLE 1-17 Example Compound NMR Spectrum 158 (S)-2-benzyloxy-N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 7.64(s, 1H), cyanophenylamino)-6-7.31(m, 5H), 7.20(m, 1H), 6.74(d, 1H), 5.75(s, 1H), propylpyrimidin-4-4.65(m, 1H), 4.57(s, 2H), 3.99(s, 2H), 3.79-3.37(m, 4H),yl]pyrrolidin-3-yl}acetamide 2.51(t, 2H), 2.32(m, 1H), 2.02(m, 1H),1.70(m, 2H), 0.98(t, 3H) 159 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ8.30(s, 1H), 7.63(s, 1H), cyanophenylamino)-6- 7.36-7.20(m, 4H), 7.02(t,1H), 6.90(d, 2H), 6.71(m, 1H), propylpyrimidin-4- 5.75(s, 1H), 4.69(m,1H), 4.51(s, 2H), 3.83-3.42(m, 4H), yl]pyrrolidin-3-yl}-2- 2.51(t, 2H),2.34(m, 1H), 2.04(m, 1H), 1.70(m, 2H), phenoxyacetamide 0.98(t, 3H) 160(S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(s, 1H), 7.60(s, 1H),cyanophenylamino)-6- 7.33(m, 2H), 7.21(d, 1H), 5.76(s, 1H), 4.65(m, 1H),3.93- propylpyrimidin-4- 3.31(m, 4H), 2.96(s, 2H), 2.49(t, 2H), 2.34(m,1H), yl]pyrrolidin-3-yl}-2- 2.28(s, 6H), 2.03(m, 1H), 1.71(m, 2H),0.97(t, 3H) (dimethylamino)acetamide 161 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz,CDCl₃) δ 8.91(s, 1H), 8.37(s, 1H), cyanophenylamino)-6- 7.62(s, 1H),7.35(t, 1H), 7.23(d, 1H), 5.75(s, 1H), propylpyrimidin-4- 4.57(m, 1H),3.74(m, 2H), 2.96(m, 2H), 2.60(m, 2H), yl]pyrrolidin-3-yl}-3- 2.50(m,2H), 2.41(m, 2H), 2.28(m, 7H), 2.00(m, 1H), (dimethylamino)propanamide1.71(q, 2H), 0.98(t, 3H) 162 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ8.36(s, 1H), 8.02(s, 1H), cyanophenylamino)-6- 7.60(d, 1H), 7.34(t, 2H),7.20(d, 1H), 5.75(s, 1H), propylpyrimidin-4- 4.56(m, 1H), 3.74-3.49(m,4H), 2.55-2.41(m, 8H), 2.35(s, yl]pyrrolidin-3-yl}-4- 6H), 2.00(m, 1H),1.86(m, 1H), 1.69(m, 2H), 0.96(t, 3H) dimethylaminobutanamide 163N-(S)-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(s, 1H), 7.63(s, 1H),cyanophenylamino)-6- 7.32(t, 1H), 7.22(m, 1H), 7.18(s, 1H), 6.72(m, 1H),propylpyrimidin-4- 5.76(s, 1H), 4.68(m, 1H), 3.95(s, 2H), 3.81(m, 2H),yl]pyrrolidin-3-yl}-2- 3.55(m, 2H), 3.41(m, 2H), 2.51(t, 2H), 2.34(m,1H), ethoxyacetamide 2.06(m, 1H), 1.71(m, 2H), 1.23(t, 3H), 0.96(t, 3H)164 N-(S)-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.35(s, 1H), 7.61(s, 1H),cyanophenylamino)-6- 7.40(s, 1H), 7.36(t, 1H), 7.20(d, 1H), 7.13(s, 1H),5.76(s, propylpyrimidin-4- 1H), 4.67(m, 1H), 4.01(s, 2H), 3.80(m, 2H),3.76(d, 2H), yl]pyrrolidin-3-yl}-2-(2- 3.66(d, 2H), 3.50(m, 2H), 3.32(s,3H), 2.49(t, 2H), methoxyethoxy)acetamide 2.33(m, 1H), 2.06(m, 1H),1.71(m, 2H), 0.98(t, 3H) 165 (S)-benzyl 2-{1-[2-(3- ¹H-NMR(400 MHz,CDCl₃) δ 8.35(s, 1H), 7.64(d, 1H), cyanophenylamino)-6- 7.34(m, 5H),7.20(d, 1H), 6.58(s, 1H), 5.70(s, 1H), propylpyrimidin-4- 5.46(m, 1H),5.12(s, 2H), 4.61(m, 1H), 3.89(m, 2H), yl]pyrrolidin-3-ylamino}-2-3.80-3.25(m, 4H), 2.48(t, 2H), 2.28(m, 1H), 2.01(m, 1H),oxoethylcarbamate 1.70(m, 2H), 0.98(t, 3H) 166 (S)-tert-butyl3-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.64(s, 1H),cyanophenylamino)-6- 7.31(t, 1H), 7.20(d, 1H), 7.11(s, 1H), 5.75(s, 1H),propylpyrimidin-4- 4.75(m, 1H), 4.61(m, 1H), 3.76-3.25(m, 4H), 3.18(m,yl]pyrrolidin-3-ylamino}-3- 2H), 2.50(m, 2H), 2.32(m, 1H), 2.27(m, 2H),2.17(m, oxobutylcarbamate 1H), 1.81(m, 2H), 1.69(m, 2H), 1.37(s, 9H),0.96(t, 3H)

TABLE 1-18 Example Compound NMR Spectrum 167 (S)-tert-butyl 4-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 7.60(s, 1H), cyanophenylamino)-6-7.34-7.27(m, 1H), 7.18(d, 1H), 5.90(m, 1H), 5.74(s, 1H),propylpyrimidin-4- 4.61(m, 1H), 4.14(m, 2H), 3.78-3.34(m, 4H), 2.72(m,yl]pyrrolidin-3- 2H), 2.23(t, 2H), 2.11(m, 2H), 2.01(m, 1H),1.81-1.71(m, ylcarbamoyl}piperidine-1- 6H), 1.45(s, 9H), 0.98(t, 3H)carboxylate 168 (R)-2-methyl-5-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 8.80(dd,1H), 7.65(dd, 1H), methylpyrrolidin-1-yl)-6- 7.44(d, 1H), 6.24(d, 1H),4.35(m, 1H), 3.90-3.45(m, 2H), propylpyrimidin-2- 2.70-2.60(m, 2H),2.52(s, 3H), 2.30-2.00(m, 3H), 1.90- ylamino]benzonitrile 1.70(m, 3H),1.40-1.20(m, 3H), 1.05(t, 3H) hydrochloride 169 (R)-2-amino-5-[4-(2-¹H-NMR(400 MHz, CD₃OD) δ 7.63(d, 1H), 7.35(dd, 1H),methylpyrrolidin-1-yl)-6- 6.85(d, 1H), 6.15(d, 1H), 4.30(m, 1H),3.80-3.40(m, 2H), propylpyrimidin-2- 2.60(t, 2H), 2.30-2.00(m, 3H),1.90-1.70(m, 3H), 1.30- ylamino]benzonitrile 1.20(m, 3H), 1.04(t, 3H)hydrochloride 170 (S)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(s,1H), 7.45(dd, 1H), (methylamino)pyrrolidin-1- 7.20-7.10(m, 2H), 5.72(s,1H), 3.90-3.10(m, 5H), 2.50- yl]-6-propylpyrimidin-2- 2.40(m, 8H),2.25-2.10(m, 1H), 1.90(brs, 1H), 1.71(q, ylamino}benzonitrile 2H),0.97(t, 3H) 171 (S)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H),7.63(brs, 1H), (ethylamino)pyrrolidin-1-yl]- 7.48(d, 1H), 7.17(d, 1H),5.71(s, 1H), 3.90-3.10(m, 5H), 6-propylpyrimidin-2- 2.80-2.70(m, 2H),2.60-2.40(m, 5H), 2.25-2.15(m, 1H), ylamino}-2- 2.00-1.80(m, 1H),1.71(q, 2H), 1.15(t, 3H), 0.98(t, 3H) methylbenzonitrile 172(S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.38(s, 1H), 7.63(dd, 1H),(ethylamino)pyrrolidin-1-yl]- 7.27(d, 1H), 5.96(s, 1H), 4.10-3.90(m,2H), 3.85-3.50(m, 6-propylpyrimidin-2- 3H), 3.17(q, 2H), 2.60-2.45(m,3H), 2.45(s, 3H), 2.30- ylamino}-2- 2.20(m, 1H), 1.74(q, 2H), 1.36(t,3H), 0.98(t, 3H) methylbenzonitrile hydrochloride 173 5-{4-[3-¹H-NMR(400 MHz, CD₃OD) δ 8.38(s, 1H), 7.63(dd, 1H),(ethylamino)pyrrolidin-1-yl]- 7.27(d, 1H), 5.96(s, 1H), 4.10-3.90(m,2H), 3.85-3.50(m, 6-propylpyrimidin-2- 3H), 3.17(q, 2H), 2.60-2.45(m,3H), 2.45(s, 3H), 2.30- ylamino}-2- 2.20(m, 1H), 1.74(q, 2H), 1.36(t,3H), 0.98(t, 3H) methylbenzonitrile hydrochloride 174(S)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.32(s, 1H), 7.63(dd,1H), (methylamino)pyrrolidin-1- 7.27(d, 2H), 5.97(s, 1H), 3.95-3.62(m,5H), 2.78(s, 3H), yl]-6-propylpyrimidin-2- 2.54-2.49(m, 3H), 2.44(s,3H), 2.28-2.23(m, 1H), 1.76- ylamino}benzonitrile 1.70(m, 2H), 0.97(t,3H) hydrochloride 175 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.65(s,1H), 7.70(d, 1H), (methylamino)pyrrolidin-1- 7.37(d, 1H), 5.77(s, 1H),4.00-3.30(m, 5H), 2.60-2.40(m, yl]-6-propylpyrimidin-2-yl}-3- 5H),2.25-2.15(m, 1H), 2.05-1.95(m, 1H), 1.70-1.60(m,nitrobenzene-1,4-diamine 2H), 0.99(t, 3H)

TABLE 1-19 Example Compound NMR Spectrum 176 (S)-N¹-{4-[3- ¹H-NMR(400MHz, CDCl₃) δ 8.64(s, 1H), 7.70(d, 1H), (ethylamino)pyrrolidin-l-yl]-7.28(d, 1H), 5.77(s, 1H), 4.00-3.30(m, 5H), 2.80-2.70(m,6-propylpyrimidin-2-yl}-3- 2H), 2.51(t, 2H), 2.30-2.20(m, 1H),2.00-1.90(m, 1H), nitrobenzene-1,4-diamine 1.72(q, 2H), 1.17(t, 3H),0.99(t, 3H) 177 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.66(s, 1H),7.76(d, 1H), (ethylamino)pyrrolidin-l-yl]- 7.47(d, 1H), 6.05(s, 1H),4.10-3.90(m, 2H), 3.80-3.50(m, 6-propylpyrimidin-2-yl}-3- 3H),3.25-3.10(m, 2H), 2.60-2.45(m, 3H), 2.30-2.20(m,nitrobenzene-1,4-diamine 1H), 1.78(q, 2H), 1.37(t, 3H), 1.00(t, 3H)hydrochloride 178 (S)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.44(s, 1H),7.79(d, 1H), (methylamino)pyrrolidin-1- 7.39(t, 1H), 7.24(d, 1H),5.99(s, 1H), 3.96(m, 2H), 3.75- yl]-6-propylpyrimidin-2- 3.65(m, 3H),2.80(s, 3H), 2.53(m, 1H + 2H), 2.26(m, 1H), ylamino}benzonitrile 1.73(m,2H), 0.99(s, 3H) hydrochloride 179 (R)-3-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ8.13(d, 1H), 7.87(dd, 1H), (aminomethyl)pyrrolidin-1- 7.60-7.45(m, 2H),6.27(d, 1H), 4.20-3.60(m, 3H), 3.50- yl]-6-propylpyrimidin-2- 3.35(m,1H), 3.20-3.00(m, 2H), 2.80-2.60(m, 3H), 2.45- ylamino}benzonitrile2.25(m, 1H), 2.00-1.90(m, 1H), 1.79(q, 2H), 1.05(t, 3H) dihydrochloride180 (S)-2-fluoro-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.90-8.80(m, 1H),8.45- (methylamino)pyrrolidin-1- 8.35(m, 1H), 7.24(t, 1H), 5.98(s, 1H),4.00-3.80(m, 2H), yl]-6-propylpyrimidin-2- 3.80-3.55(m, 3H), 2.79(s,3H), 2.55-2.45(m, 3H), 2.30- ylamino}benzonitrile 2.20(m, 1H), 1.74(q,2H), 0.98(t, 3H) hydrochloride 181 (S)-2-fluoro-5-{4-[3- ¹H-NMR(400 MHz,CD₃OD) δ 8.40(brs, 1H), 7.90-7.75(m, (ethylamino)pyrrolidin-1-yl]- 1H),7.24(t, 1H), 5.98(s, 1H), 4.10-3.85(m, 2H), 3.85- 6-propylpyrimidin-2-3.50(m, 3H), 3.18(q, 2H), 2.60-2.40(m, 3H), 2.30-2.20(m,ylamino}benzonitrile 1H), 1.74(q, 2H), 1.36(t, 3H), 0.98(t, 3H)hydrochloride 182 5-[4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ8.20-8.00(m, 1H), 7.95- yl)-6-propylpyrimidin-2- 7.85(m, 1H), 7.42(t,1H), 6.32(s, 1H), 4.20-3.60(m, 5H), ylamino]-2- 2.68(t, 2H),2.60-2.40(m, 1H), 2.30-2.15(m, 1H), 1.90- fluorobenzonitrile 1.70(m,2H), 1.06(t, 3H) dihydrochloride 183 N-(4-fluorophenyl)-4- ¹H-NMR(400MHz, CDCl₃) δ 7.63-7.58(m, 2H), 7.00- methyl-6-(pyrrolidin-1- 6.95(m,3H), 5.59(s, 1H), 3.53-3.41(m, 4H), 2.25(s, 3H), yl)pyrimidin-2-amine1.99(brs, 4H) 184 (3R,5S)-1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 7.48(dd,2H), 6.97(dd, 2H), fluorophenyl)-6- 5.66(s, 1H), 4.56(s, 1H), 4.41(d,1H), 3.78(d, 1H), 3.62- propylpyrimidin-4-yl]-5- 3.45(m, 4H), 2.43(dd,2H), 2.13(brs, 1H), 1.97(brs, 1H), (hydroxymethyl)pyrrolidin-3-1.71-1.65(m, 2H), 0.96(t, 3H) ol 185 (S)-{1-[2-(1H-indol-6- ¹H-NMR(400MHz, CDCl₃) δ 8.40(brs, 1H), 8.05(s, 1H), ylamino)-6-propylpyrimidin-7.49(d, 1H), 7.04(dd, 1H), 6.97(dd, 1H), 6.90(brs, 1H),4-yl]pyrrolidin-2-yl}methanol 6.43(d, 1H), 5.70(s, 1H), 4.39(brs, 1H),3.75(dd, 1H), 3.59(dd, 1H), 3.46(brs, 1H), 3.35-3.27(m, 1H), 2.48(dd,2H), 2.04-1.96(m, 3H), 1.78-1.69(m, 3H), 0.97(t, 3H)

TABLE 1-20 Example Compound NMR Spectrum 186 (R)-{1-[2-(1H-indol-6-¹H-NMR(400 MHz, CDCl₃) δ 8.49(brs, 1H), 8.03(s, 1H),ylamino)-6-propylpyrimidin- 7.48(d, 1H), 7.01-6.80(m, 3H), 6.42(s, 1H),5.69(s, 1H), 4-yl]pyrrolidin-2-yl}methanol 4.86(brs, 1H), 4.38(brs, 1H),3.74(dd, 1H), 3.57(dd, 1H), 3.44(brs, 1H), 3.29(brs, 1H), 2.48(dd, 2H),2.04-1.96(m, 3H), 1.77-1.68(m, 3H), 0.96(t, 3H) 187{1-[2-(1H-indol-6-ylamino)- ¹H-NMR(400 MHz, CDCl₃) δ 8.49(brs, 1H),8.02(s, 1H), 6-propylpyrimidin-4- 7.47(dd, 1H), 7.02-6.89(m, 3H),6.42(d, 1H), 5.69(s, 1H), yl]pyrrolidin-2-yl}methanol 4.86(brs, 1H),4.38(brs, 1H), 3.75(dd, 1H), 3.57(dd, 1H), 3.43(brs, 1H), 3.29(brs, 1H),2.47(dd, 2H), 2.04-1.96(m, 3H), 1.77-1.68(m, 3H), 0.98(t, 3H) 188(R)-N-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.49(brs, 1H), 8.19(brs, 1H),(methoxymethyl)pyrrolidin- 7.48(d, 1H), 7.10(dd, 1H), 7.01-6.92(m, 2H),6.45(d, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 5.69(s, 1H), 4.53(brs, 1H),3.94(brs, 1H), 3.47(d, 1H), 1H-indol-6-amine 3.37(s, 3H), 3.31-3.16(m,2H), 2.47(dd, 2H), 2.11- 2.00(m, 4H), 1.76-1.69(m, 2H), 0.99(t, 3H) 189(S)-N-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.48(brs, 1H), 8.22(brs, 1H),(methoxymethyl)pyrrolidin- 7.48(d, 1H), 7.10(dd, 1H), 7.01-6.92(m, 2H),6.46(d, 1H), 1-yl]-6-propylpyrimidin-2-yl}- 5.69(s, 1H), 4.53(brs, 1H),3.94(brs, 1H), 3.47(d, 1H), 1H-indol-6-amine 3.36(s, 3H), 3.31-3.16(m,2H), 2.47(dd, 2H), 2.11- 2.00(m, 4H), 1.76-1.69(m, 2H), 0.99(t, 3H) 190N-[4-(2-methylpyrrolidin-1- ¹H-NMR(400 MHz, CDCl₃) δ 8.14(brs, 1H),8.04(brs, 1H), yl)-6-propylpyrimidin-2-yl]- 7.49(d, 1H), 7.11-7.08(m,3H), 6.47(dd, 1H), 5.67(s, 1H), 1H-indol-6-amine 4.28(brs, 1H),3.59(brs, 1H), 3.42(brs, 1H), 2.47(dd, 2H), 2.12-1.98(m, 4H),1.79-1.72(m, 2H), 1.27(dd, 3H), 0.99(t, 3H) 191 (S)-methyl1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ 8.56(brs, 1H), 8.31(brs, 1H),ylamino)-6-propylpyrimidin- 7.45(dd, 1H), 7.12(dd, 1H), 7.00(s, 1H),6.45(dd, 1H), 4-yl]pyrrolidine-2- 5.74(brs, 1H), 4.75(brs, 1H), 3.63(s,3H), 3.65-3.45(d, carboxylate 1H), 2.48(dd, 2H), 2.32-2.02(m, 4H),1.75-1.70(m, 2H), 0.99(dd, 3H) 192 N-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz,CDCl₃) δ 8.68(brs, 1H), 8.10(brs, 1H), ylamino)-6-propylpyrimidin-7.47(d, 1H), 7.11(s, 1H), 7.04(s, 1H), 6.46(s, 1H), 4-yl]pyrrolidin-3-5.48(brs, 1H), 4.55(s, 1H), 3.82-3.44(m, 5H), 2.38- yl}acetamide 2.23(m,3H), 2.03(s, 3H), 2.05-1.95(m, 1H), 1.75-1.68(m, 2H), 0.99(dd, 3H) 193(S)-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ 12.25(brs, 1H),9.81-9.78(m, ylamino)-6-propylpyrimidin- 2H), 8.22(s, 1H), 7.37(d, 1H),7.16(dd, 1H), 6.80(d, 1H), 4-yl]pyrrolidin-2-yl}methanol 6.37(s, 1H),5.10(s, 1H), 4.70(brs, 1H), 4.50(brs, 1H), hydrochloride 4.06(d, 1H),3.69(dd, 1H), 3.31(dd, 1H), 3.20-3.13(m, 1H), 2.30-1.98(m, 6H),1.58-1.50(m, 2H), 0.93(t, 3H) 194 (S)-3-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ8.31(s, 1H), 7.58(dd, 1H), (hydroxymethyl)pyrrolidin-1- 7.34(t, 1H),7.24(d, 1H), 7.22(brs, 1H), 5.81(s, 1H), yl]-6-propylpyrimidin-2-4.41(br, 1H), 3.73(m, 2H), 3.52(br, 1H), 3.39(m, 1H),ylamino}benzonitrile 2.51(t, 2H), 2.11-2.00(m, 3H), 1.88(br, 1H),1.75(m, 2H), 0.99(t, 3H) 195 (S)-(1-{2-[3- ¹H-NMR(400 MHz, CDCl₃) δ10.30-10.13(br, 1H), 7.84(s, (methylthio)phenylamino]-6- 1H), 7.25(m,2H), 6.98(s, 1H), 5.71(brs, 1H), 4.45(br, propylpyrimidin-4- 1H),3.89(br, 1H), 3.68(br, 2H), 3.43(br, 1H), 2.70(br,yl}pyrrolidin-2-yl)methanol 2H), 2.49(s, 3H), 2.18(br, 1H), 2.08(m, 3H),1.77(m, 2H), 1.00(m, 3H)

TABLE 1-21 Example Compound NMR Spectrum 196 (S)-{1-[2-(4-chloro-3-¹H-NMR(400 MHz, CDCl₃) δ 8.87(s, 1H), 7.37(m, 2H), nitrophenylamino)-6-7.34(br, 1H), 5.82(s, 1H), 4.44(br, 1H), 3.77(m, 2H), propylpyrimidin-4-3.52(br, 1H), 3.39(br, 1H), 2.50(t, 2H), 2.07(m, 3H),yl]pyrrolidin-2-yl}methanol 1.94(m, 1H), 1.74(m, 2H), 1.00(t, 3H) 197(S)-{1-[2-(1H-indol-5- ¹H-NMR(400 MHz, CDCl₃) δ 8.29(brs, 1H), 7.80(s,1H), ylamino)-6-propylpyrimidin- 7.27(m, 3H), 7.13(m, 1H), 6.47(s, 1H),5.69(s, 1H), 4-yl]pyrrolidin-2-yl}methanol 3.59(m, 2H), 3.48(br, 1H),3.38(br, 1H), 2.49(t, 2H), 1.97(m, 3H), 1.75(m, 3H), 1.99(t, 3H) 198(S)-{1-[2-(1H- ¹H-NMR(400 MHz, CDCl₃) δ 8.84(s, 1H), 8.24(m, 2H),benzo[d]imidazol-5- 8.01(s, 1H), 7.56(d, 1H), 6.71(d, 1H), 6.06(s, 1H),ylamino)-6-propylpyrimidin- 4.57(br, 1H), 3.95(br, 1H), 3.72(m, 1H),3.56(m, 1H), 4-yl]pyrrolidin-2-yl}methanol 3.40(br, 1H), 2.63(m, 2H),2.10(m, 3H), 1.82(m, 3H), 1.03(t, 3H) 199 (S)-(1-{6-propyl-2-[2-¹H-NMR(400 MHz, CDCl₃) δ 8.42(brs, 1H), 7.59(d, 1H),(trifluoromethyl)-1H- 7.44(d, 1H), 7.38(d, 1H), 6.88(d, 1H), 6.84(s,1H), benzo[d]imidazol-5- 5.93(brs, 1H), 3.76(br, 1H), 3.55(br, 1H),3.35(s, 2H), ylamino]pyrimidin-4- 2.50(t, 2H), 2.11(m, 2H), 2.02(m, 2H),1.77(m, 2H), yl}pyrrolidin-2-yl)methanol 1.02(t, 3H) 200 (S)-{1-[2-(4-¹H-NMR(400 MHz, CDCl₃) δ 9.98(br, 1H), 7.45(br, 2H),methoxyphenylamino)-6- 6.84(d, 2H), 6.10-5.67(br, 1H), 4.38(br, 1H),3.78(s, 3H), propylpyrimidin-4- 3.73(m, 2H), 3.59(br, 1H), 3.42(br, 1H),2.52(m, 2H), yl]pyrrolidin-2-yl}methanol 2.15(br, 1H), 2.05(m, 3H),1.75(m, 2H), 0.97(t, 3H) 201 (S)-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ10.45(br, 1H), 7.92(s, 1H), chlorophenylamino)-6- 7.36(br, 1H), 7.22(m,1H), 7.03(m, 1H), 5.73(br, 1H), propylpyrimidin-4- 4.47(br, 1H), 4.13(m,2H), 3.83(br, 1H), 3.43(br, 1H), yl]pyrrolidin-2-yl}methanol 2.51(m,2H), 2.09(m, 4H), 1.75(m, 2H), 0.97(t, 3H) 202 (S)-{1-[2-(3- ¹H-NMR(400MHz, CDCl₃) δ 10.17(br, 1H), 7.61(brs, 1H), methoxyphenylamino)-6-7.21(m, 1H), 7.04(br, 1H), 6.63(m, 1H), 5.70(brs, 1H),propylpyrimidin-4- 4.42(br, 1H), 3.90(br, 1H), 3.81(s, 3H), 3.75(m, 2H),yl]pyrrolidin-2-yl}methanol 3.40(m, 1H), 2.53(m, 2H), 2.09(m, 4H),1.76(m, 2H), 0.97(t, 3H) 203 (S)-(1-{6-propyl-2-[3- ¹H-NMR(400 MHz,CDCl₃) δ 10.62(br, 1H), 8.32(m, 1H), (trifluoromethyl)phenyl- 7.57(d,1H), 7.41(brs, 1H), 7.33(m, 1H), 6.22-5.78(br, amino]pyrimidin- 1H),4.50(br, 1H), 4.13(m, 1H), 3.93(m, 2H), 3.46(br, 4-yl}pyrrolidin- 1H),2.53(br, 2H), 2.28-2.05(m, 4H), 1.77(m, 2H), 0.97(t, 2-yl)methanol 3H)204 (S)-{1-[2-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.08(s, 1H), 7.09(d,1H), methylphenylamino)-6- 6.95(d, 1H), 5.76(s, 1H), 4.33(br, 1H),3.71-3.61(m, 2H), propylpyrimidin-4- 3.40(br, 1H), 3.39(br, 1H), 2.52(m,2H), 2.30(s, 3H), yl]pyrrolidin-2-yl}methanol 2.11-2.00(m, 4H), 1.77(m,2H), 1.00(t, 3H) 205 (S)-{1-[2-(5-methoxy-2- ¹H-NMR(400 MHz, CDCl₃) δ9.31(br, 1H), 7.64(s, 1H), methylphenylamino)-6- 7.09(d, 1H), 6.62(m,1H), 5.72(s, 1H), 4.27(br, 1H), propylpyrimidin-4- 3.82(s, 3H), 3.77(m,1H), 3.46(m, 2H), 3.36(m, 1H), yl]pyrrolidin-2-yl}methanol 2.56(m, 2H),2.31(s, 3H), 2.06-1.99(m, 4H), 1.80(m, 2H), 1.02(t, 3H)

TABLE 1-22 Example Compound NMR Spectrum 206 (S)-{1-[2-(3-chloro-4-¹H-NMR(400 MHz, CDCl₃) δ 10.11(br, 1H), 7.91(d, 1H),methylphenylamino)-6- 7.23(br, 1H), 7.13(m, 1H), 6.14-5.73(br, 1H),4.46(br, propylpyrimidin-4- 1H), 3.81(m, 2H), 3.63(br, 1H), 3.38(br,1H), 2.52(m, yl]pyrrolidin-2-yl}methanol 2H), 2.32(s, 3H), 2.10(m, 4H),1.78(m, 2H), 0.98(t, 3H) 207 (S)-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ9.15(s, 1H), 8.37(br, 1H), nitrophenylamino)-6- 7.83(d, 1H), 7.81(d,1H), 7.41(t, 1H), 5.83(s, 1H), propylpyrimidin-4- 4.67(br, 1H), 4.13(m,1H), 3.80(m, 1H), 3.56(br, 1H), yl]pyrrolidin-2-yl}methanol 3.42(br,1H), 2.53(m, 2H), 2.17-2.05(m, 4H), 1.79(m, 2H), 1.00(t, 3H) 208(S)-{1-[2-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.95(s, 1H), 7.85(br,1H), nitrophenylamino)-6- 7.50(m, 1H), 7.16(t, 1H), 5.81(s, 1H),4.49(br, 1H), propylpyrimidin-4- 4.45(br, 1H), 3.76(m, 2H), 3.53-3.39(m,2H), 2.48(m, yl]pyrrolidin-2-yl}methanol 2H), 2.13(m, 3H), 1.75(m, 2H),0.97(t, 3H) 209 (S)-{1-[6-propyl-2-(quinolin- ¹H-NMR(400 MHz, CDCl₃) δ8.75(d, 1H), 8.38(d, 1H), 6-ylamino)pyrimidin-4- 8.09(d, 1H), 8.00(d,1H), 7.72(dd, 1H), 7.33(m, 1H), yl]pyrrolidin-2-yl}methanol 5.81(s, 1H),4.49(br, 1H), 3.75(m, 2H), 3.55(m, 1H), 3.42(m, 1H), 2.54(m, 2H),2.07(m, 3H), 1.91(m, 1H), 1.78(m, 2H), 1.02(t, 3H) 210(S)-{1-[2-(4-methyl-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.65(s, 1H), 7.56(s,1H), nitrophenylamino)-6- 7.28(d, 1H), 6.01(s, 1H), 4.43-3.50(m, 5H),2.53(m, 5H), propylpyrimidin-4- 2.12-2.02(m, 4H), 1.73(m, 2H), 1.00(t,3H) yl]pyrrolidin-2-yl}methanol 211 (S)-(1-{2-[4-amino-3- ¹H-NMR(400MHz, CD₃OD) δ 7.77(brs, 1H), 7.34(d, 1H), (trifluoromethyl)phenylamino]-6.85(d, 1H), 6.12(brs, 1H), 4.13(m, 1H), 3.93-3.50(m,6-propylpyrimidin-4- 4H), 2.57(t, 2H), 2.09-1.98(m, 4H), 1.74(m, 2H),1.03(t, yl}pyrrolidin-2-yl)methanol 3H) 212 (S)-{1-[2-(4-amino-3-¹H-NMR(400 MHz, CDCl₃) δ 8.82(s, 1H), 7.25(m, 1H), nitrophenylamino)-6-6.82(brs, 1H), 6.74(d, 1H), 5.94(s, 2H), 5.74(s, 1H), propylpyrimidin-4-4.52(s, 1H), 3.75(m, 1H), 3.63(m, 1H), 3.49(m, 1H),yl]pyrrolidin-2-yl}methanol 3.37(s, 1H), 2.47(t, 2H), 2.02(m, 3H),1.90(m, 1H), 1.72(m, 2H), 0.98(t, 3H) 213 (S)-5-{4-[2- ¹H-NMR(400 MHz,CDCl₃) δ 8.21(s, 1H), 7.45(d, 1H), (hydroxymethyl)pyrrolidin-1- 7.18(d,1H), 6.97(brs, NH), 5.79(s, 1H), 4.41(s, 1H), yl]-6-propylpyrimidin-2-3.71(m, 2H), 3.51(m, 1H), 3.38(s, 1H), 2.48(m, 5H), ylamino}-2- 2.02(m,3H), 1.86(s, 1H), 1.70(m, 2H), 0.99(t, 3H) methylbenzonitrile 214(S)-2-fluoro-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.22(m, 1H), 7.58(m, 1H),(hydroxymethyl)pyrrolidin-1- 7.12(s, 1H), 7.07(t, 1H), 5.81(s, 1H),4.39(s, 1H), 3.73(m, yl]-6-propylpyrimidin-2- 2H), 3.51(s, 1H), 3.38(s,1H), 2.52(t, 2H), 2.02(m, 3H), ylamino}benzonitrile 1.84(s, 1H), 1.74(m,2H), 0.99(t, 3H) 215 (S)-2-amino-5-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ7.83(s, 1H), 7.33(d, 1H), (hydroxymethyl)pyrrolidin-1- 6.76(d, 1H),5.80(s, 1H), 4.42(m, 3H), 3.75(m, 3H), yl]-6-propylpyrimidin-2- 2.55(m,2H), 2.07(m, 4H), 1.78(m, 2H), 1.00(t, 3H) ylamino}benzonitrile

TABLE 1-23 Example Compound NMR Spectrum 216(S)-{1-[6-propyl-2-(quinolin- ¹H-NMR(400 MHz, CDCl₃) δ 8.94(s, 1H),8.66(d, 1H), 3-ylamino)pyrimidin-4- 7.99(d, 1H), 7.72(d, 1H),7.55-7.45(m, 2H), 7.25(br, 1H), yl]pyrrolidin-2-yl}methanol 5.80(s, 1H),4.40(br, 1H), 3.75(m, 2H), 3.51(m, 1H), 3.40(m, 1H), 2.51(m, 2H),2.04(m, 3H), 1.95(m, 1H), 1.77(m, 2H), 0.98(t, 3H) 217(S)-{1-[2-(indolin-6- ¹H-NMR(400 MHz, CDC1₃) δ 7.21(s, 1H), 7.00(d, 1H),ylamino)-6-propylpyrimidin- 6.83(brs, 1H), 6.69(d, 1H), 5.69(s, 1H),4.37(s, 1H), 4-yl]pyrrolidin-2-yl}methanol 3.76(m, 1H), 3.62(m, 1H),3.55(m, 1H), 3.46(m, 1H), 3.32(m, 1H), 2.96(t, 2H), 2.46(t, 2H), 2.00(m,3H), 1.83(m, 1H), 1.69(m, 2H), 0.97(t, 3H) 218 (S)-3-{4-[3- ¹H-NMR(400MHz, CD₃OD) δ 8.19(d, 1H), 7.82-7.75(m, (cyclohexylamino)pyrrolidin-1H), 7.61-7.54(m, 2H), 6.35(s, 1H), 4.23-3.74(m, 5H),1-yl]-6-propylpyrimidin-2- 3.23(brs, 1H), 2.69(dd, 2H), 2.60(brs, 1H),2.35-2.20(m, ylamino}benzonitrile 1H), 1.90(d, 2H), 1.85-1.72(m, 5H),1.47-1.25(m, 5H), dihydrochloride 1.06(t, 3H) 219 (S)-3-{4-[3-¹H-NMR(400 MHz, CD₃OD) δ 8.25(brs, 1H), 7.79(brs,(isopropylamino)pyrrolidin- 1H), 7.60-7.52(m, 2H), 6.32(s, 1H),4.21-3.75(m, 5H), 1-yl]-6-propylpyrimidin-2- 3.58-3.52(m, 1H), 2.68(dd,2H), 2.60(brs, 1H), 2.32(brs, ylamino}benzonitrile 1H), 1.85-1.75(m,2H), 1.42(dd, 6H), 1.06(t, 3H) dihydrochloride 220 (S)-3-{4-[3-¹H-NMR(400 MHz, CD₃OD) δ 8.15(d, 1H), 7.82(s, 1H),(aminoethylamino)pyrrolidin- 7.60-7.54(m, 2H), 6.35(s, 1H), 4.18-3.75(m,5H), 3.44- 1-yl]-6-propylpyrimidin-2- 3.40(m, 2H), 3.31-3.25(m, 2H),2.69(dd, 2H), 2.67- ylamino}benzonitrile 2.49(m, 1H), 2.40-2.25(m, 1H),1.83-1.76(m, 2H), 1.06(t, dihydrochloride 3H) 221(S)-3-{4-[3-(piperidin-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.20(brs, 1H),7.57(brs, ylamino)pyrrolidin-1-yl]-6- 1H), 7.38(dd, 1H), 7.22(d, 1H),5.87(s, 1H), 4.15-3.31(m, propylpyrimidin-2- 7H), 3.01-2.94(m, 3H),2.48(dd, 2H), 2.31-2.18(m, 2H), ylamino}benzonitrile 2.11(d, 1H),1.91(brs, 1H), 1.75-1.68(m, 2H), 1.57- 1.46(m, 2H), 0.97(t, 3H) 222(S)-3-{4-[3-(1-butylpiperidin- ¹H-NMR(400 MHz, CD₃OD) δ 8.55-8.45(m,1H), 7.32- 4-ylamino)pyrrolidin-1-yl]-6- 7.26(m, 1H), 7.39(dd, 1H),7.23(d, 1H), 5.89(s, 1H), propylpyrimidin-2- 3.99-3.44(m, 6H), 2.99(d,2H), 2.65(brs, 1H), 2.49(dd, ylamino}benzonitrile 2H), 2.39-2.28(m, 3H),2.10-1.94(m, 4H), 1.85-1.69(m, 2H), 1.55-1.28(m, 6H), 1.00-0.87(m, 6H)223 (S)-N-{1-[6-butyl-2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.25(brs, 1H),7.61(brs, 1H), cyanophenylamino)pyrimidin- 7.33-7.28(m, 2H), 7.17(d,1H), 6.17(brs, 1H), 5.73(s, 4-yl]pyrrolidin-3- 1H), 4.58(brs, 1H),3.92-3.33(m, 4H), 2.49(dd, 2H), 2.30- yl}acetamide 2.25(m, 1H),2.04-2.00(m, 1H), 2.00(s, 3H), 1.69-1.61(m, 2H), 1.43-1.33(m, 2H),0.94(t, 3H) 224 (S)-3-{4-butyl-6-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.31(s,1H), 7.58(dd, 1H), (hydroxymethyl)pyrrolidin-1- 7.34(dd, 1H), 7.22(d,1H), 7.17(brs, 1H), 5.81 (s, 1H), yl]pyrimidin-2- 4.88-4.30(m, 2H),3.75-3.69(m, 2H), 3.51(brs, 1H), ylamino}benzonitrile 3.38(brs, 1H),2.53(dd, 2H), 2.11-2.00(m, 3H), 1.86(brs, 1H), 1.73-1.65(m, 2H),1.45-1.37(m, 2H), 0.94(t, 3H) 225 (R)-3-[4-butyl-6-(2- ¹H-NMR(400 MHz,CDCl₃) δ 8.48(brs, 1H), 7.51(d, 1H), methylpyrrolidin-1- 7.33-7.25(m,2H), 7.19(d, 1H), 5.74(s, 1H), 4.37-3.38(m, yl)pyrimidin-2- 3H),2.49(dd, 2H), 2.08-2.01(m, 3H), 1.78-1.75(m, 1H), ylamino]benzonitrile1.71-1.63(m, 2H), 1.44-1.36(m, 2H), 1.29(brs, 3H), 0.94(t, 3H)

TABLE 1-24 Example Compound NMR Spectrum 226 (S)-3-{4-butyl-6-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.56(dd, 1H),(methylamino)pyrrolidin-1- 7.33-7.28(m, 2H), 7.17(d, 1H), 5.74(s, 1H),3.78-3.16(m, yl]pyrimidin-2- 5H), 2.50(s, 3H), 2.48(dd, 2H),2.22-2.17(m, 1H), ylamino}benzonitrile 1.91(brs, 1H), 1.70-1.62(m, 2H),1.43-1.34(m, 2H), 0.94(t, 3H) 227 (S)-tert-butyl 1-[6-butyl-2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.30(brs, 1H), 7.61(brs, 1H),cyanophenylamino)pyrimidin- 7.33(dd, 1H), 7.20(d, 1H), 7.13(brs, 1H),5.74(s, 1H), 4-yl]pyrrolidin-3- 4.80(brs, 1H), 4.34(brs, 1H),3.82-3.33(m, 4H), 2.50(dd, ylcarbamate 2H), 2.29-2.23(m, 1H), 1.99(brs,1H), 1.70-1.63(m, 2H), 1.46(s, 9H), 1.42-1.34(m, 2H), 0.95(t, 3H) 228(S)-N-{1-[6-butyl-2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.19(brs, 1H),7.48(brs, 1H), cyano-4- 7.16(d, 1H), 7.06(brs, 1H), 6.01(brs, 1H),5.71(s, 1H), methylphenylamino)pyrimidin- 4.60-4.56(m, 1H), 3.75-3.38(m,4H), 2.48(dd, 2H), 4-yl]pyrrolidin-3- 2.45(s, 3H), 2.32-2.24(m, 1H),2.04-2.00(m, 1H), 2.00(s, yl}acetamide 3H), 1.69-1.61(m, 2H),1.43-1.34(m, 2H), 0.94(t, 3H) 229 (S)-5-{4-butyl-6-[2- ¹H-NMR(400 MHz,CDCl₃) δ 8.20(dd, 1H), 7.45(dd, 1H), (hydroxymethyl)pyrrolidin-1-7.18(d, 1H), 7.11(brs, 1H), 5.78(s, 1H), 4.40(brs, 1H),yl]pyrimidin-2-ylamino}-2- 3.74-3.69(m, 2H), 3.50(brs, 1H), 3.37(brs,1H), 2.51(dd, methylbenzonitrile 2H), 2.47(s, 3H), 2.08-1.99(m, 3H),1.86(brs, 1H), 1.72- 1.64(m, 2H), 1.42-1.37(m, 2H), 0.94(t, 3H) 230(R)-5-[4-butyl-6-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, 1H), 7.40(brs,1H), methylpyrrolidin-1- 7.16(d, 1H), 7.03(brs, 1H), 5.72(s, 1H),4.40-3.36(m, yl)pyrimidin-2-ylamino]-2- 3H), 2.48(dd, 2H), 2.47(s, 3H),2.12-2.00(m, 3H), 1.77- methylbenzonitrile 1.75(m, 1H), 1.70-1.62(m,2H), 1.44-1.36(m, 2H), 1.29(brs, 3H), 0.94(t, 3H) 231(S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(d, 1H), 7.44(dd, 1H),(methylamino)pyrrolidin-1- 7.16(d, 1H), 7.11(brs, 1H), 5.72(s, 1H),3.78-3.16(m, yl]pyrimidin-2-ylamino}-2- 5H), 2.50(s, 3H), 2.48(dd, 2H),2.47(s, 3H), 2.22-2.16(m, methylbenzonitrile 1H), 1.90(brs, 1H),1.70-1.62(m, 2H), 1.43-1.34(m, 2H), 0.94(t, 3H) 232 (S)-tert-butyl1-[6-butyl-2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.20(brs, 1H), 7.50(brs, 1H),cyano-4- 7.17(d, 1H), 7.16(brs, 1H), 5.70(s, 1H), 4.90(brs, 1H),methylphenylamino)pyrimidin- 4.33(brs, 1H), 3.82-3.33(m, 4H), 2.49(dd,2H), 2.47(s, 4-yl]pyrrolidin-3- 3H), 2.27-2.23(m, 1H), 1.99(brs, 1H),1.69-1.62(m, 2H), ylcarbamate 1.46(s, 9H), 1.43-1.33(m, 2H), 0.95(t, 3H)233 (S)-3-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CDCl₃) δ 8.19(brs, 1H),7.48(brs, 1H), 1-yl)-6-butylpyrimidin-2- 7.16(d, 1H), 7.06(brs, 1H),6.01(brs, 1H), 5.71(s, 1H), ylamino]benzonitrile 4.60-4.56(m, 1H),3.75-3.38(m, 4H), 2.48(dd, 2H), dihydrochloride 2.45(s, 3H),2.32-2.24(m, 1H), 2.04-2.00(m, 1H), 2.00(s, 3H), 1.69-1.61(m, 2H),1.43-1.34(m, 2H), 0.94(t, 3H) 234 (S)-5-[4-(3-aminopyrrolidin-¹H-NMR(400 MHz, CDCl₃) δ 8.19(brs, 1H), 7.48(brs, 1H),1-yl)-6-butylpyrimidin-2- 7.16(d, 1H), 7.06(brs, 1H), 6.01(brs, 1H),5.71(s, 1H), ylamino]-2- 4.60-4.56(m, 1H), 3.75-3.38(m, 4H), 2.48(dd,2H), methylbenzonitrile 2.45(s, 3H), 2.32-2.24(m, 1H), 2.04-2.00(m, 1H),2.00(s, dihydrochloride 3H), 1.69-1.61(m, 2H), 1.43-1.34(m, 2H), 0.94(t,3H) 235 (S)-3-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.38(s, 1H),7.58(d, 1H), (isopropylamino)pyrrolidin- 7.33(dd, 1H), 7.20(d, 1H),7.17(brs, 1H), 5.73(s, 1H), 1-yl]pyrimidin-2- 3.90-3.38(m, 5H),2.99-2.93(m, 1H), 2.50(dd, 2H), 2.28- ylamino}benzonitrile 2.21(m, 1H),1.85(brs, 1H), 1.71-1.63(m, 2H), 1.44- 1.37(m, 2H), 1.11(t, 6H), 0.97(t,3H)

TABLE 1-25 Example Compound NMR Spectrum 236 (S)-3-{4-butyl-6-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.45(brs, 1H), 7.53(brs, 1H),(diethylamino)pyrrolidin-1- 7.32(dd, 1H), 7.21(d, 1H), 7.09(brs, 1H),5.74(s, 1H), yl]pyrimidin-2- 4.04-3.35(m, 5H), 2.72(brs. 4H), 2.51(dd,2H), 2.24(brs, ylamino}benzonitrile 1H), 1.93(brs, 1H), 1.71-1.64(m,2H), 1.44-1.35(m, 2H), 1.05(t, 3H), 1.11(t, 6H), 0.97(t, 3H) 237(S)-3-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.57(d, 1H),(cyclopropylmethylamino)pyrrolidin- 7.33(dd, 1H), 7.21(d, 1H), 7.11(brs,1H), 5.74(s, 1H), 1-yl]pyrimidin-2- 3.91-3.14(m, 6H), 2.63-2.48(m. 4H),2.26-2.18(m, 1H), ylamino}benzonitrile 1.90(brs, 1H), 1.71-1.63(m, 2H),1.44-1.35(m, 2H), 1.25- 0.93(m, 4H), 0.53(dd, 2H), 0.15(d, 2H) 238(S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.30(s, 1H), 7.47(d, 1H),(isopropylamino)pyrrolidin- 7.17(d, 1H), 7.08(brs, 1H), 5.71(s, 1H),3.90-3.05(m, 1-yl]pyrimidin-2-ylamino}-2- 5H), 2.99-2.93(m, 1H),2.49(dd, 2H), 2.47(s, 3H), 2.28- methylbenzonitrile 2.20(m, 1H),1.84(brs, 1H), 1.70-1.63(m, 2H), 1.44- 1.34(m, 2H), 1.11(dd, 6H),0.97(t, 3H) 239 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs,1H), 7.42(brs, 1H), (diethylamino)pyrrolidin-1- 7.16(d, 1H), 7.05(brs,1H), 5.71(s, 1H), 4.04-3.18(m, yl]pyrimidin-2-ylamino}-2- 5H), 2.71(brs.4H), 2.49(dd, 2H), 2.47(s, 3H), 2.23- methylbenzonitrile 1.92(m, 2H),1.71-1.63(m, 2H), 1.44-1.35(m, 2H), 1.07(dd, 6H), H), 0.97(t, 3H) 240(S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(s, 1H), 7.45(d, 1H),(cyclopropylmethylamino)pyrrolidin- 7.17(d, 1H), 7.09(brs, 1H), 5.71(s,1H), 3.90-3.05(m, 1-yl]pyrimidin-2- 5H), 2.56-2.48(m, 7H), 2.25-2.18(m,1H), 1.89(brs, 1H), ylamino}-2- 1.70-1.63(m, 2H), 1.44-1.36(m, 2H),1.25-0.93(m, 4H), methylbenzonitrile 0.53(dd, 2H), 0.15(d, 2H) 241(S)-N-{1-[2-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.89(brs, 1H),8.10(brs, 1H), nitrophenylamino)-6- 7.35(s, 2H), 6.21(brs, 1H), 5.74(s,1H), 4.63-4.59(m, propylpyrimidin-4- 1H), 4.10-3.38(m, 4H), 2.47(dd,2H), 2.34-2.28(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.09-2.04(m, 1H),2.03(s, 3H), 1.74-1.68(m, 2H), 0.97(t, 3H) 242 (S)-N-(1-{2-[3-¹H-NMR(400 MHz, CDCl₃) δ 7.78(s, 1H), 7.29(dd, 1H),(methylthio)phenylamino]-6- 7.18(dd, 1H), 7.01(brs, 1H), 6.84(d, 1H),5.96(d, 1H), propylpyrimidin-4- 5.67(s, 1H), 4.59-4.56(m, 1H),4.73-3.48(m, 4H), 2.68(s, yl}pyrrolidin-3-yl)acetamide 3H), 2.46(dd,2H), 2.44-2.21(m, 1H), 2.06-2.00(m, 1H), 2.03(s, 3H), 1.76-1.66(m, 2H),0.97(t, 3H) 243 (S)-N-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CDCl₃) δ8.15(s, 1H), 7.49(d, 1H), ylamino)-6-propylpyrimidin- 7.11(dd, 1H),7.00(d, 1H), 6.47(s, 1H), 5.95(brs, 1H), 4-yl]pyrrolidin-3- 5.62(s, 1H),4.55(brs, 1H), 3.75-3.49(m, 4H), 2.45(dd, yl}acetamide 2H), 2.29-2.23(m,1H), 2.06-2.00(m, 1H), 2.03(s, 3H), 1.75-1.66(m, 2H), 0.96(t, 3H) 244(S)-N-(1-{6-propyl-2-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.44(brs, 1H), 7.46(d,1H), (trifluoromethyl)phenylamino]pyrimidin- 7.35(dd, 1H), 7.19(d, 2H),5.88(d, 1H), 5.72(s, 1H), 4.62- 4-yl}pyrrolidin-3- 4.58(m, 1H),3.75-3.49(m, 4H), 2.47(dd, 2H), 2.24- yl)acetamide 2.33(m, 1H),2.06-2.00(m, 1H), 2.00(s, 3H), 1.76-1.67(m, 2H), 0.95(t, 3H) 245(S)-N-{1-[2-(4-methyl-2-oxo- ¹H-NMR(400 MHz, CDCl₃) δ 8.08(brs, 1H),7.38(d, 1H), 2H-chromen-7-ylamino)-6- 7.35(dd, 1H), 6.99(brs, 1H),6.98(d, 1H), 5.94(brs, 1H), propylpyrimidin-4- 5.72(s, 1H), 4.69(brs,1H), 3.72-3.49(m, 4H), 2.45(dd, yl]pyrrolidin-3-yl}acetamide 2H),2.33(s, 3H), 2.33-2.24(m, 1H), 2.06-2.00(m, 1H), 2.03(s, 3H),1.75-1.67(m, 2H), 0.99(t, 3H)

TABLE 1-26 Example Compound NMR Spectrum 246 (S)-N{1-[2-(3-chloro-4-¹H-NMR(400 MHz, CDCl₃) δ 7.97(brs, 1H), 7.20(d, 1H),methylphenylamino)-6- 7.09(d, 1H), 7.00(brs, 1H), 6.15(d, 1H), 5.65(s,1H), propylpyrimidin-4- 4.59(brs, 1H), 3.70-3.48(m, 4H), 2.45(dd, 2H),2.30(s, yl]pyrrolidin-3-yl}acetamide 3H), 2.28-2.23(m, 2H), 2.00(s, 3H),1.72-1.66(m, 2H), 0.96(t, 3H) 247 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃)δ 9.27(brs, 1H), 7.76(dd, 1H), nitrophenylamino)-6- 7.45(brs, 1H),7.37(brs, 1H), 7.24(brs, 1H), 5.89(s, 1H), propylpyrimidin-4- 5.76(s,1H), 4.64-4.60(m, 1H), 3.86-3.32(m, 4H), yl]pyrrolidin-3-yl}acetamide2.48(dd, 2H), 2.36-2.28(m, 1H), 2.08-2.02(m, 1H), 2.02(s, 3H),1.75-1.68(m, 2H), 0.98(t, 3H) 248 (S)-N-{1-[2-(4-fluoro-3- ¹H-NMR(400MHz, CDCl₃) δ 9.05(brs, 1H), 7.43(brs, 1H), nitrophenylamino)-6-7.13(dd, 1H), 6.56(brs, 1H), 5.74(s, 1H), 4.64-4.61(m,propylpyrimidin-4- 1H), 3.83-3.43(m, 4H), 2.47(dd, 2H), 2.32(brs, 1H),2.12- yl]pyrrolidin-3-yl}acetamide 2.05(m, 1H), 2.05(s, 3H),1.75-1.67(m, 2H), 0.98(t, 3H) 249 (S)-N-{1-[2-(4-methyl-3- ¹H-NMR(400MHz, CDCl₃) δ 8.93(brs, 1H), 7.82(brs, 1H), nitrophenylamino)-6- 7.33(d,1H), 7.17(d, 1H), 6.38(brs, 1H), 5.69(s, 1H), propylpyrimidin-4-4.62-4.58(m, 1H), 3.76-3.48(m, 4H), 2.51(s, 3H),yl]pyrrolidin-3-yl}acetamide 2.45(dd, 2H), 2.32-2.26(m, 1H),2.08-2.02(m, 1H), 2.02(s, 3H), 1.73-1.67(m, 2H), 0.96(t, 3H) 250(S)-benzyl 5-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.52(brs, 1H), 7.41-7.33(m,acetamidopyrrolidin-1-yl)-6- 5H), 7.18(d, 1H), 7.10(brs, 1H), 6.78(d,1H), 5.93(s, 1H), propylpyrimidin-2-ylamino]- 5.64(s, 1H), 5.18(s, 2H),4.55(brs, 1H), 3.82(s, 3H), 3.76- 2-methoxyphenylcarbamate 3.48(m, 4H),2.45(dd, 2H), 2.26-2.20(m, 1H), 2.04- 1.96(m, 1H), 1.97(s, 3H),1.73-1.66(m, 2H), 0.97(t, 3H) 251 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400MHz, CDCl₃) δ 8.21(brs, 1H), 7.61(brs, 2H), fluorophenylamino)-6-7.09(dd, 1H), 6.07(brs, 1H), 5.74(s, 1H), 4.60(d, 1H),propylpyrimidin-4- 3.76-3.39(m, 4H), 2.48(dd, 2H), 2.33-2.28(m, 1H),2.08- yl]pyrrolidin-3-yl}acetamide 2.02(m, 1H), 2.02(s, 3H),1.76-1.67(m, 2H), 0.98(t, 3H) 252 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400MHz, CDCl₃) δ 8.20(brs, 1H), 7.49(brs, 2H), methylphenylamino)-6-7.27(brs, 1H), 7.18(d, 1H), 5.99(d, 1H), 5.71(s, 1H), propylpyrimidin-4-4.62-4.58(m, 1H), 3.75-3.41(m, 4H), 2.47(dd, 2H),yl]pyrrolidin-3-yl}acetamide 2.46(s, 3H), 2.32-2.27(m, 1H), 2.08-2.02(m,1H), 2.01(s, 3H), 1.74-1.68(m, 2H), 0.97(t, 3H) 253(S)-N-(1-{2-[4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, 1H),7.44(brs, 2H), (trifluoromethyl)phenylamino]- 7.08(dd, 1H), 5.91(brs,1H), 5.72(s, 1H), 4.62-4.58(m, 6-propylpyrimidin-4- 1H), 3.75-3.39(m,4H), 2.47(dd, 2H), 2.32-2.25(m, 1H), yl}pyrrolidin-3-yl)acetamide2.08-2.01(m, 1H), 2.01(s, 3H), 1.76-1.66(m, 2H), 0.97(t, 3H) 254(S)-N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.97(brs, 1H),7.24(brs, 1H), nitrophenylamino)-6- 6.98(brs, 1H), 6.73(d, 1H), 6.06(d,1H), 5.92(brs, 2H), propylpyrimidin-4- 5.67(s, 1H), 4.61-4.57(m, 1H),3.79-3.44(m, 4H), yl]pyrrolidin-3-yl}acetamide 2.44(dd, 2H),2.32-2.27(m, 1H), 2.08-2.01(m, 1H), 2.00(s, 3H), 1.75-1.65(m, 2H),0.97(t, 3H) 255 (S)-N-{1-[2-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ8.59(brs, 1H), 7.07(d, 1H), methylphenylamino)-6- 6.86(dd, 1H),6.68(brs, 1H), 6.22(s, 1H), 5.68(s, 1H), propylpyrimidin-4- 4.58(s, 1H),3.71-3.33(m, 5H), 2.47(dd, 2H), 2.30- yl]pyrrolidin-3-yl}acetamide2.20(m, 2H), 2.27(s, 3H), 2.00(s, 3H), 1.73-1.68(m, 2H), 0.98(t, 3H)

TABLE 1-27 Example Compound NMR Spectrum 256 (S)-3-[4-(3- ¹H-NMR(400MHz, CD₃OD) δ 8.33(s, 1H), 7.82(d, 1H), acetamidopyrrolidin-1-yl)-6-7.42(d, 1H), 7.35(t, 1H), 5.89(s, 1H), 4.50-4.40(m, 1H),propylpyrimidin-2- 3.90-3.30(m, 4H), 2.49(t, 2H), 2.30-2.20(m, 1H),2.10- ylamino]benzamide 1.90(m, 4H), 1.73(q, 2H), 0.99(t, 3H) 257(S)-3-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.29(s, 1H), 7.80(s, 1H),acetamidopyrrolidin-1-yl)-6- 7.33(d, 2H), 5.87(s, 1H), 4.47(t, 1H),3.90-3.30(m, 4H), propylpyrimidin-2-yl]amino}- 2.91 (s, 3H), 2.48(t,2H), 2.35-2.20(m, 1H), 2.10-2.00(m, N-methylbenzamide 1H), 1.95(s, 3H),1.72(q, 2H), 1.00(t, 3H) 258 (S)-N-[1-(2-{[3- ¹H-NMR(400 MHz, CD₃OD) δ7.03(t, 1H), 6.80-6.55(m, (aminomethyl)phenyl]amino}- 3H), 5.85(s, 1H),4.50-4.35(m, 3H), 3.80-3.40(m, 4H), 6-propylpyrimidin-4- 2.47(t, 2H),2.30-2.15(m, 1H), 2.05-1.95(m, 1H), 1.94(s, yl)pyrrolidin-3-yl]acetamide3H), 1.68(q, 2H), 0.98(t, 3H) 259 (S)-3-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ7.35-7.20(m, 2H), 7.07(d, acetamidopyrrolidin-1-yl)-6- 1H), 6.28(brs,1H), 4.55-4.35(m, 1H), 3.85-3.40(m, 4H), propylpyrimidin-2-yl]amino}-2.51(t, 2H), 2.40-2.15(m, 1H), 2.15-1.90(m, 1H), 1.94(s,4-chlorobenzamide 3H), 1.68(q, 2H), 0.95(t, 3H) 260(S)-N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ 7.48(d, 1H),7.44-7.40(m, cyanophenylamino)-6- 1H), 6.84(d, 1H), 6.13(d, 1H),4.52-4.43(m, 1H), 3.86- propylpyrimidin-4- 3.44(m, 4H), 2.63-2.59(m,2H), 2.33-2.25(m, 1H), 2.10- yl]pyrrolidin-3-yl}acetamide 2.02(m, 1H),1.96(d, 3H), 1.78-1.73(m, 2H), 1.03(t, 3H) hydrochloride 261(S)-N-(1-{2-[4-amino-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.05-7.91(m, 2H),7.33(dd, (trifluoromethyl)phenylamino]- 1H), 6.72(dd, 1H), 5.53(d, 1H),4.72(brs, 1H), 4.19(brs, 6-propylpyrimidin-4- 2H), 4.03-3.50(m, 4H),2.37-2.23(m, 4H), 2.11(s, 3H), yl}pyrrolidin-3-yl)acetamide 1.68-1.53(m,2H), 0.98(t, 3H) hydrochloride 262 (S)-N-{1-[2-(3-amino-5- ¹H-NMR(400MHz, CD₃OD) δ 7.15(d, 1H), 7.13(s, 1H), cyanophenylamino)-6- 6.67(s,1H), 6.15(d, 1H), 4.54-4.47(m, 1H), 3.97-3.46(m, propylpyrimidin-4- 4H),2.65-2.60(m, 2H), 2.41-2.30(m, 1H), 2.16-2.08(m,yl]pyrrolidin-3-yl}acetamide 1H), 1.97(s, 3H), 1.81-1.74(m, 2H), 1.04(t,3H) hydrochloride 263 (S)-N-{1-[2-(1H-indol-6- ¹H-NMR(400 MHz, CD₃OD) δ7.75(s, 1H), 7.54(d, 1H), ylamino)-6-propylpyrimidin- 7.26(s, 1H),7.01(t, 1H), 6.45(s, 1H), 6.09(d, 1H), 4.47(d, 4-yl]pyrrolidin-3- 1H),4.00-3.50(m, 4H), 2.59(q, 2H), 2.40-2.20(m, 1H), yl}acetamidehydrochloride 2.20-2.00(m, 1H), 1.96(s, 3H), 1.80-1.60(m, 2H), 1.03(t,3H) 264 (S)-N-{1-[2-(5-chloro-2- ¹H-NMR(400 MHz, CD₃OD) δ 7.76(d, 1H),7.35-7.15(m, methylphenylamino)-6- 2H), 6.21(d, 1H), 4.45(d, 1H),3.90-3.50(m, 4H), 2.62(t, propylpyrimidin-4- 2H), 2.40-2.15(m, 4H),2.15-1.85(m, 4H), 1.76(q, 2H), yl]pyrrolidin-3-yl}acetamide 1.05(t, 3H)hydrochloride 265 (S)-N-(1-{2-[4-fluoro-3- ¹H-NMR(400 MHz, CD₃OD) δ8.16(d, 1H), 7.77(brs, 1H), (trifluoromethyl)phenylamino]- 7.38(t, 1H),6.26(d, 1H), 4.48(d, 1H), 3.90-3.45(m, 4H), 6-propylpyrimidin-4- 2.65(t,2H), 2.40-2.20(m, 1H), 2.20-2.00(m, 1H), 1.95(s,yl}pyrrolidin-3-yl)acetamide 3H), 1.76(q, 2H), 1.05(t, 3H) hydrochloride

TABLE 1-28 Example Compound NMR Spectrum 266 (S)-N-{1-[2-(3-amino-4-¹H-NMR(400 MHz, CD₃OD) δ 7.05(brs, 1H), 6.94(t, 1H),fluorophenylamino)-6- 6.76(t, 1H), 6.13(d, 1H), 4.47(d, 1H),4.00-3.40(m, 4H), propylpyrimidin-4- 2.65-2.50(m, 2H), 2.40-2.20(m, 1H),2.20-2.00(m, 1H), yl]pyrrolidin-3-yl}acetamide 1.95(s, 3H), 1.75(q, 2H),1.03(t, 3H) hydrochloride 267 (S)-N-(1-{6-propyl-2-[3- ¹H-NMR(400 MHz,CD₃OD) δ 8.17(d, 1H), 7.80-7.70(m,(trifluoromethyl)phenylamino]pyrimidin- 1H), 7.59(t, 1H), 7.47(d, 1H),6.26(d, 1H), 4.60-4.40(m, 4-yl}pyrrolidin-3-yl)acetamide 1H),4.00-3.40(m, 4H), 2.66(t, 2H), 2.40-2.20(m, 1H), hydrochloride2.20-2.00(m, 1H), 1.95(s, 3H), 1.78(q, 2H), 1.05(t, 3H) 268(S)-N-(1-{2-[3-amino-5- ¹H-NMR(400 MHz, CD₃OD) δ 7.29(d, 1H), 7.01(d,1H), (trifluoromethyl)phenylamino]- 6.74(s, 1H), 6.21(d, 1H),4.60-4.40(m, 1H), 4.00-3.40(m, 6-propylpyrimidin-4- 4H), 2.63(t, 2H),2.40-2.20(m, 1H), 2.20-2.00(m, 1H), yl}pyrrolidin-3-yl)acetamide 1.95(s,3H), 1.77(q, 2H), 1.04(t, 3H) hydrochloride 269 (S)-N-{1-[2-(3-¹H-NMR(400 MHz, CD₃OD) δ 8.92(d, 1H), 8.04(d, 1H), nitrophenylamino)-6-7.81(t, 1H), 7.63(t, 1H), 6.30(d, 1H), 4.60-4.45(m, 1H),propylpyrimidin-4- 4.10-3.40(m, 4H), 2.75-2.60(m, 2H), 2.45-2.25(m, 1H),yl]pyrrolidin-3-yl}acetamide 2.20-2.00(m, 1H), 1.96(s, 3H), 1.90-1.70(m,2H), 1.06(t, hydrochloride 3H) 270 (S)-N-(1-{2-[(4- ¹H-NMR(400 MHz,CD₃OD) δ 7.90-7.75(m, 2H), 7.50- aminophenyl)amino]-6- 7.40(m, 2H),6.26(d, 1H), 4.50-4.35(m, 1H), 4.00-3.40(m, propylpyrimidin-4- 4H),2.66(q, 2H), 2.40-2.20(m, 1H), 2.20-2.00(m, 1H),yl}pyrrolidin-3-yl)acetamide 1.96(s, 3H), 1.90-1.70(m, 2H), 1.05(t, 3H)hydrochloride 271 (S)-N-(1-{2-[(4-chloro-3- ¹H-NMR(400 MHz, CD₃OD) δ7.28(d, 1H), 7.24(d, 1H), hydroxyphenyl)amino]-6- 7.01(s, 1H), 6.20(d,1H), 4.49(d, 1H), 4.00-3.40(m, 4H), propylpyrimidin-4- 2.63(t, 2H),2.40-2.20(m, 1H), 2.20-2.00(m, 1H), 1.96(s, yl}pyrrolidin-3-yl)acetamide3H), 1.76(q, 2H), 1.03(t, 3H) hydrochloride 272 (S)-4-{[4-(3- ¹H-NMR(400MHz, CD₃OD) δ 7.18(t, 1H), 6.98(d, 1H), acetamidopyrrolidin-1-yl)-6-6.62(d, 1H), 6.17(d, 1H), 4.49(d, 1H), 4.00-3.40(m, 4H),propylpyrimidin-2-yl]amino}- 2.62(t, 2H), 2.40-2.20(m, 1H), 2.20-2.00(m,1H), 1.95(s, 2-hydroxybenzoic acid 3H), 1.76(q, 2H), 1.04(1, 3H)hydrochloride 273 (S)-5-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.15(d, 1H),7.71(s, 1H), acetamidopyrrolidin-1-yl)-6- 6.93(d, 1H), 6.14(d, 1H),4.47(d, 1H), 4.10-3.40(m, 4H), propylpyrimidin-2-yl]amino}- 2.62(t, 2H),2.55-2.30(m, 1H), 2.30-2.00(m, 1H), 1.95(s, 2-hydroxybenzoic acid 3H),1.04(q, 3H) hydrochloride 274 (S)-N-(1-{2-[(3-hydroxy-4- ¹H-NMR(400 MHz,CD₃OD) δ 7.50(s, 1H), 7.10(brs, 1H), methylphenyl)amino]-6- 6.95(d, 1H),6.70(brs, 1H), 6.61(s, 1H), 5.59(s, 1H), propylpyrimidin-4- 4.12(brs,1H), 3.80-3.30(m, 4H), 2.44(t, 2H), 2.18(s, 3H),yl}pyrrolidin-3-yl)acetamide 2.15-1.95(m, 2H), 1.91(s, 3H), 1.66(q, 2H),0.92(t, 3H) 275 (S)-N-(1-{2-[(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ7.96(s, 1H), 7.21(d, 1H), hydroxyphenyl)amino]-6- 6.92(d, 1H), 5.72(brs,1H), 5.68(s, 1H), 4.12(d, 1H), propylpyrimidin-4- 3.80-3.20(m, 4H),2.46(t, 2H), 2.35-2.20(m, 1H), 2.00- yl}pyrrolidin-3-yl)acetamide1.90(m, 4H), 1.70(q, 2H), 0.97(t, 3H)

TABLE 1-29 Example Compound NMR Spectrum 276 (S)-N-(1-{2-[(4-hydroxy-3-¹H-NMR(400 MHz, CDCl₃) δ 7.24(s, 1H), 6.85(brs, 1H),methylphenyl)amino]-6- 6.70(d, 1H), 6.26(d, 1H), 5.59(s, 1H), 4.52(brs,1H), propylpyrimidin-4- 3.80-3.20(m, 4H), 2.43(t, 2H), 2.25-2.10(m, 1 +3H), 2.00- yl}pyrrolidin-3-yl)acetamide 1.85(m, 1 + 3H), 1.67(q, 2H),0.94(t, 3H) 277 (S)-N-(1-{2-[(3-fluoro-4- ¹H-NMR(400 MHz, CDCl₃) δ7.75(d, 1H), 6.95(d, 1H), hydroxyphenyl)amino]-6- 6.89(t, 1H), 6.10(brs,1H), 5.63(s, 1H), 4.59(brs, 1H), propylpyrimidin-4- 3.90-3.30(m, 4H),2.45(t, 2H), 2.35-2.15(m, 1H), 2.10- yl}pyrrolidin-3-yl)acetamide2.00(m, 1H), 1.99(s, 3H), 1.68(q, 2H), 0.96(t, 3H) 278(S)-N-(1-{2-[(3-hydroxy-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.43(s, 1H),7.10-7.00(m, methoxyphenyl)amino]-6- 1H), 6.78(d, 1H), 5.62(s, 1H),4.59(s, 1H), 3.86(s, 3H), propylpyrimidin-4- 3.80-3.20(m, 4H), 2.45(t,2H), 2.35-2.20(m, 1H), 2.10- yl}pyrrolidin-3-yl)acetamide 2.00(m, 1H),2.01(s, 3H), 1.67(q, 2H), 0.96(t, 3H) 279 (S)-N-(1-{2-[(3-methoxy-4-¹H-NMR(400 MHz, CDCl₃) δ 7.56(s, 1H), 7.38(brs, 1H),methylphenyl)amino]-6- 7.00(d, 1H), 6.89(d, 1H), 5.78(brs, 1H), 5.65(s,1H), propylpyrimidin-4- 4.59(brs, 1H), 3.83(s, 3H), 3.80-3.20(m, 4H),2.46(t, 2H), yl}pyrrolidin-3-yl)acetamide 2.40-2.20(m, 2H), 2.16(s, 3H),1.99(s, 3H), 1.71(q, 2H), 0.97(t, 3H) 280 (S)-N-[1-(2-{[4-methyl-3-¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, 1H), 7.37(d, 1H),(trifluoromethyl)phenyl]amino}- 7.21(brs, 1H), 7.16(d, 1H), 5.70(s, 1H),4.60(brs, 1H), 6-propylpyrimidin-4- 3.85-3.20(m, 4H), 2.46(t, 2H),2.41(s, 3H), 2.35-2.20(m, yl)pyrrolidin-3-yl]acetamide 1H), 2.15-2.00(m,1H), 1.98(s, 3H), 1.71(q, 2H), 0.97(t, 3H) 281 (S)-N-(1-{2-[(3,4-¹H-NMR(400 MHz, CDCl₃) δ 7.50-7.40(m, 2H), 7.04(d,dimethylphenyl)amino]-6- 1H), 5.73(brs, 1H), 5.65(s, 1H), 4.62(brs, 1H),3.85- propylpyrimidin-4- 3.20(m, 4H), 2.46(t, 2H), 2.40-2.25(m, 1H),2.24(s, 3H), yl}pyrrolidin-3-yl)acetamide 2.21(s, 3H), 2.15-2.00(m, 1H),2.00(s, 3H), 1.71(q, 2H), 0.97(t, 3H) 282 (S)-N-(1-{2-[(3-fluoro-4-¹H-NMR(400 MHz, CDCl₃) δ 7.73(d, 1H), 7.16(brs, 1H),methylphenyl)amino]-6- 7.10-7.00(m, 2H), 5.74(brs, 1H), 5.68(s, 1H),4.61(brs, propylpyrimidin-4- 1H), 3.85-3.20(m, 4H), 2.47(t, 2H),2.40-2.25(m, 1H), yl}pyrrolidin-3-yl)acetamide 2.21(s, 3H), 2.10-1.90(m,4H), 1.71(q, 2H), 0.97(t, 3H) 283 (S)-N-{1-[2-(4-fluoro-3- ¹H-NMR(400MHz, CDCl₃) δ 11.06(d, 1H), 8.98(d, 1H), nitrophenylamino)-6- 7.55(d,1H), 7.22(d, 1H), 6.78(s, 1H), 5.79(s, 1H), 4.68(s, propylpyrimidin-4-1H), 4.05-3.59(m, 4H), 2.56-2.51(m, 2H), 2.40-2.21(m,yl]pyrrolidin-3-yl}acetamide 2H), 2.05(s, 3H), 1.82-1.76(m, 2H),0.98-0.94(m, 3H) hydrochloride 284 (S)-N-{1-[2-(4-methyl-3- ¹H-NMR(400MHz, CDCl₃) δ 8.78(d, 1H), 7.70-7.60(m, nitrophenylamino)-6- 1H),7.38-7.34(m, 1H), 7.24-7.21(m, 1H), 5.73(d, 1H), propylpyrimidin-4-4.73(brs, 1H), 4.08-3.70(m, 4H), 2.53(s, 3H), 2.46-yl]pyrrolidin-3-yl}acetamide 2.27(m, 4H), 2.11(s, 3H), 1.78-1.68(m, 2H),0.98-0.94(m, hydrochloride 3H) 285 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400MHz, CDCl₃) δ 12.85(d, 1H), 10.66(d, 1H), methylphenylamino)-6-8.10-7.88(m, 2H), 7.61-7.54(m, 1H), 7.29-7.24(m, 1H), propylpyrimidin-4-5.73(s, 1H), 4.73(s, 1H), 4.06-3.73(m, 4H), 2.63(brs,yl]pyrrolidin-3-yl}acetamide 1H), 2.48(s, 3H), 2.44-2.28(m, 4H), 2.12(s,3H), 1.73- hydrochloride 1.65(m, 2H), 0.97-0.93(m, 3H)

TABLE 1-30 Example Compound NMR Spectrum 286 (S)-N-{1-[2-(4-amino-3-¹H-NMR(400 MHz, CD₃OD) δ 8.66(s, 0.5H), 8.57(s, nitrophenylamino)-6-0.5H), 7.46-7.42(m, 1H), 7.03(d, 1H), 6.18(s, 0.5H), propylpyrimidin-4-6.14(s, 0.5H), 4.54-4.48(m, 1H), 3.92-3.60(m, 4H), 2.65-yl]pyrrolidin-3-yl}acetamide 2.60(m, 2H), 2.30-2.22(m, 1H), 2.13-2.05(m,1H), 2.00(s, hydrochloride 1.5H), 1.99(s, 1.5H), 1.80-1.74(m, 2H),1.07-1.02(m, 3H) 287 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.34(brs,1H), 7.59(brs, 1H), cyanophenylamino)-6- 7.34(dd, 1H), 7.22(d, 1H),6.98(brs, 1H), 5.76(s, 1H), propylpyrimidin-4- 5.66(d, 1H), 4.64-4.57(m,1H), 3.77-3.35(m, 4H), yl]pyrrolidin-3-yl}acetamide 2.48(dd, 2H),2.36-2.29(m, 1H), 2.05-2.01(m, 1H), hydrochloride 2.01(s, 3H),1.75-1.69(m, 2H), 0.98(t, 3H) 288 (S)-N-{1-[2-(4-chloro-3- ¹H-NMR(400MHz, CD₃OD) δ 8.66(s, 0.5H), 8.55(s, nitrophenylamino)-6- 0.5H),7.73-7.64(m, 2H), 6.32(s, 0.5H), 6.28(s, 0.5H), propylpyrimidin-4-4.53-4.50(m, 1H), 3.90-3.52(m, 4H), 2.70-2.65(m, 2H),yl]pyrrolidin-3-yl}acetamide 2.33-2.25(m, 1H), 2.15-2.07(m, 1H), 1.97(s,3H), 1.82- hydrochloride 1.76(m, 2H), 1.07-1.03(m, 3H) 289(S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.10(d, 1H), 6.97(dd,1H), methoxyphenylamino)-6- 6.72(d, 1H), 5.95(brs, 1H), 5.62(s, 1H),4.58(brs, 1H), propylpyrimidin-4- 3.82(s, 3H), 3.84-3.60(m, 6H),2.44(dd, 2H), 2.28- yl]pyrrolidin-3-yl}acetamide 2.23(m, 1H),2.02-1.95(m, 1H), 2.00(s, 3H), 1.74-1.65(m, 2H), 0.97(t, 3H) 290(S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.24(d, 1H),7.12-7.04(m, chlorophenylamino)-6- 2H), 6.93-6.89(m, 1H), 5.98(brs, 1H),5.69(s, 1H), propylpyrimidin-4- 4.58(brs, 1H), 3.97(s, 2H), 3.75-3.36(m,4H), 2.46(dd, yl]pyrrolidin-3-yl}acetamide 2H), 2.30-2.24(m, 1H),2.06-1.96(m, 1H), 1.99(s, 3H), 1.74-1.68(m, 2H), 1.00(t, 3H) 291(S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.25(d, 1H),6.91-6.87(m, fluorophenylamino)-6- 2H), 5.72(d, 1H), 5.67(s, 1H),5.60-4.55(m, 1H), 3.72(s, propylpyrimidin-4- 2H), 3.84-3.36(m, 4H),2.46(dd, 2H), 2.31-2.26(m, 1H), yl]pyrrolidin-3-yl}acetamide2.06-1.96(m, 1H), 2.00(s, 3H), 1.75-1.66(m, 2H), 0.97(t, 3H) 292(S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.14(d, 1H),6.95-6.89(m, methylphenylamino)-6- 3H), 5.96(d, 1H), 5.63(s, 1H),5.60-4.55(m, 1H), 3.84- propylpyrimidin-4- 3.36(m, 6H), 2.44(dd, 2H),2.28-2.23(m, 1H), 2.12(s, yl]pyrrolidin-3-yl}acetamide 3H), 2.02-1.95(m,1H), 2.00(s, 3H), 1.72-1.67(m, 2H), 0.97(t, 3H) 293 N-{1-[2-(4-amino-3-¹H-NMR(400 MHz, CD₃OD) δ 8.62 (s, 0.5H), 8.51(s, nitrophenylamino)-6-0.5H), 7.41(brs, 1H), 6.99(d, 1H), 6.16(s, 1H), 4.49(d,propylpyrimidin-4- 1H), 3.83-3.44(m, 4H), 2.62(brs, 2 H), 2.34-2.27(m,1H), yl]pyrrolidin-3-yl}acetamide 2.11-2.01(m, 1H), 1.96(s, 3H),1.78-1.74(m, 2H), 1.04(t, hydrochloride 3H) 294 N-{1-[2-(3- ¹H-NMR(400MHz, CD₃OD) δ 8.73(brs, NH), 8.32(s, 1H), cyanophenylamino)-6- 7.65(m,1H), 7.33(m, 1H), 7.20(m, 1H), 6.14(brs, NH), propylpyrimidin-4- 5.70(s,1H), 4.61(m, 1H), 3.76(m, 4H), 2.47(t, 2H), yl]pyrrolidin-3-yl}acetamide2.30(m, 1H), 2.02(m, 4H), 1.69(m, 2H), 0.98(t, 3H) 295 N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 9.18(s, 1H), 8.10(brs, NH),nitrophenylamino)-6- 7.76(d, 1H), 7.47(m, 1H), 7.34(m, 1H), 6.24(brs,NH), propylpyrimidin-4- 5.72(s, 1H), 4.63(m, 1H), 3.80-3.64(m, 4H),2.47(t, 2H), yl]pyrrolidin-3-yl}acetamide 2.33(m, 1H), 2.03(m, 4H),1.71(m, 2H), 0.98(t, 3H)

TABLE 1-31 Example Compound NMR Spectrum 296 N-{1-[2-(4-fluoro-3-¹H-NMR(400 MHz, CDCl₃) δ 9.08(s, 1H), 8.10(brs, NH),nitrophenylamino)-6- 7.45(m, 1H), 7.13(m, 1H), 5.98(brs, NH), 5.75(s,1H), propylpyrimidin-4- 4.62(m, 1H), 3.79-3.44(m, 4H), 2.49(t, 2H),2.33(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.03(m, 4H), 1.70(m, 2H),0.98(t, 3H) 297 N-{1-[2-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.95(s,1H), 7.81(brs, NH), nitrophenylamino)-6- 7.35(m, 2H), 5.94(brs, NH),5.74(s, 1H), 4.60(m, 1H), propylpyrimidin-4- 3.76-3.40(m, 4H), 2.47(t,2H), 2.31(m, 1H), 2.06(m, 4H), yl]pyrrolidin-3-yl}acetamide 1.70(m, 2H),0.95(t, 3H) 298 N-{1-[2-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.15(brs, NH),7.51(s, 1H), methoxyphenylamino)-6- 7.16(t, 1H), 7.02(d, 1H), 6.72(brs,NH), 6.53(d, 1H), propylpyrimidin-4- 5.53(s, 1H), 4.63(m, 1H), 3.80(s,3H), 3.70(m, 4H), yl]pyrrolidin-3-yl}acetamide 2.39(t, 2H), 2.25(m, 1H),2.04(m, 4H), 1.65(m, 2H), 0.95(t, 3H) 299 N-{1-[2-(5-methoxy-2-¹H-NMR(400 MHz, CDCl₃) δ 7.91(s, 1H), 7.05(d, 1H), methylphenylamino)-6-6.54(d, 1H), 5.63(s, 1H), 4.62(m, 1H), 3.78(s, 3H), 3.72-propylpyrimidin-4- 3.60(m, 4H), 2.46(4t, 2H), 2.30(s, 3H), 2.21(m, 1H),yl]pyrrolidin-3-yl}acetamide 2.05(m, 4H), 1.67(m, 2H), 0.95(t, 3H) 300N-{1-[2-(4- ¹H-NMR(400 MHz, CDCl₃) δ 8.29(brs, NH), 7.53(d, 2H),methoxyphenylamino)-6- 6.85(m, 2H + NH), 5.53(s, 1H), 4.66(m, 1H),3.77(s, 3H), propylpyrimidin-4- 3.71-3.51(m, 4H), 2.39(t, 2H), 2.25(m,1H), 2.05(m, 4H), yl]pyrrolidin-3-yl}acetamide 1.62(m, 2H), 0.94(t, 3H)301 N-(1-{6-propyl-2-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.60(brs, NH), 8.37(s,1H), (trifluoromethyl)phenylamino]pyrimidin- 7.50(m, 1H), 7.37(t, 1H),7.22(m, 1H), 6.85(brs, NH), 4-yl}pyrrolidin-3-yl)acetamide 5.65(s, 1H),4.66(m, 1H), 3.75-3.60(m, 4H), 2.39(t, 2H), 2.26(m, 1H), 2.11(m, 1H),2.04(s, 3H), 1.66(m, 2H), 0.94(t, 3H) 302 N-{1-[2-(3- ¹H-NMR(400 MHz,CDCl₃) δ 8.42(brs, NH), 7.91(s, 1H), chlorophenylamino)-6- 7.33(d, 1H),7.18(t, 1H), 6.94(d, 1H), 6.74(brs, NH), propylpyrimidin-4- 5.58(s, 1H),4.66(m, 1H), 3.73-3.70(m, 4H), 2.42(t, 2H), yl]pyrrolidin-3-yl}acetamide2.29(m, 1H), 2.11(m, 1H), 2.06(s, 3H), 1.64(m, 2H), 0.96(t, 3H) 303N-{1-[2-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.43(s, 1H), 7.06(d, 1H),methylphenylamino)-6- 6.90(d, 1H), 6.31(brs, NH), 5.68(s, 1H), 4.62(m,1H), propylpyrimidin-4- 3.73-3.44(m, 4H), 2.48(t, 2H), 2.31(s, 3H),2.24(m, 1H), yl]pyrrolidin-3-yl}acetamide 2.01(m, 4H), 1.70(m, 2H),0.98(t, 3H) 304 N-{1-[2-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.52(brs,NH), 7.86(s, 1H), methylphenylamino)-6- 7.27(m, 1H), 7.10(d, 1H),7.05(brs, NH), 5.52(s, 1H), propylpyrimidin-4- 4.65(m, 1H), 3.70(m, 4H),2.37(m, 2H), 2.28(s, 3H), yl]pyrrolidin-3-yl}acetamide 2.26(m, 1H),2.13(m, 1H), 2.07(s, 3H), 1.63(m, 2H), 0.95(t, 3H) 305 N-(1-{2-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.13(brs. NH), 7.73(s, 1H),(methylthio)phenylamino]-6- 7.30(d, 1H), 7.18(t, 1H), 6.85(d, 1H),6.57(brs, NH), propylpyrimidin-4- 5.57(s, 1H), 4.63(m, 1H), 3.72(m, 4H),2.48(s, 3H), yl}pyrrolidin-3-yl)acetamide 2.39(t, 2H), 2.26(m, 1H),2.04(m, 4H), 1.64(m, 2H), 0.94(t, 3H)

TABLE 1-32 Example Compound NMR Spectrum 306 N-{1-[2-(1H-indol-5-¹H-NMR(400 MHz, CDCl₃) δ 8.11(s, NH), 7.98(s, 1H),ylamino)-6-propylpyrimidin- 7.37(d, 1H), 7.35(m, 1H), 7.30(m, 1H),7.17(m, 1H), 4-yl]pyrrolidin-3- 6.99(brs, NH), 6.49(s, 1H), 5.75(brs,NH), 5.64(s, 1H), yl}acetamide 4.60(m, 1H), 3.81-3.43(m, 4H), 2.48(t,2H), 2.25(m, 1H), 1.98(m, 4H), 1.71(m, 2H), 0.98(t, 3H) 307N-(1-{6-propyl-2-[2- ¹H-NMR(400 MHz, CDCl₃) δ 8.60(brs, 1H), 7.64(s,1H), (trifluoromethyl)-1H- 7.53(brs, 1H), 7.10(s, 1H), 6.12(s, 1H),5.68(s, 1H), benzo[d]imidazol-5- 4.47(m, 1H), 3.92-3.54(m, 4H), 2.48(m,2H), 2.27(m, ylamino]pyrimidin-4- 1H), 2.01(m, 4H), 1.71(m, 2H), 0.98(t,3H) yl}pyrrolidin-3-yl)acetamide 308 N-{1-[6-propyl-2-(quinolin-6-¹H-NMR(400 MHz, CDCl₃) δ 8.67(s, 1H), 8.28(s, 1H), ylamino)pyrimidin-4-7.91(m, 2H), 7.64(m, 1H), 7.31(brs, NH), 7.24(m, 1H),yl]pyrrolidin-3-yl}acetamide 6.80(brs, NH), 5.65(s, 1H), 4.63(m, 1H),3.71-3.54(m, 4H), 2.50(t, 2H), 2.23(m, 1H), 2.04(m, 4H), 1.70(m, 2H),0.98(t, 3H) 309 N-{1-[2-(4-methyl-2-oxo-2H- ¹H-NMR(400 MHz, CD₃OD) δ8.22(m, 1H), 7.65(d, 1H), chromen-7-ylamino)-6- 7.46(m, 1H), 6.13(s,1H), 5.93(s, 1H), 4.49(m, 1H), 3.80- propylpyrimidin-4- 3.55(m, 4H),2.53(t, 2H), 2.49(s, 3H), 2.29(m, 1H), yl]pyrrolidin-3-yl}acetamide2.10(m, 1H), 1.96(s, 3H), 1.73(m, 2H), 0.99(t, 3H) 310N-{1-[6-propyl-2-(quinolin-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.98(s, 1H),8.58(s, 1H), ylamino)pyrimidin-4- 7.97(d, 1H), 7.66(m, 2H), 7.52-7.46(m,2H), 5.80(brs, yl]pyrrolidin-3-yl}acetamide NH), 5.53(s, 1H), 4.63(m,1H), 3.71-3.57(m, 4H), 2.44(t, 2H), 2.27(m, 1H), 2.05(m, 4H), 1.68(m,2H), 0.97(t, 3H) 311 N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ8.33(m, 1H), 7.59-7.50(d, cyanophenylamino)-6- 1H), 7.39(m, 1H), 6.84(d,1H), 6.13(d, 1H), 4.49(m, 1H), propylpyrimidin-4- 3.86(m, 1H), 3.68(m,2H), 3.45(m, 1H), 2.61(m, 2H), yl]pyrrolidin-3-yl}acetamide 2.27(m, 1H),2.04(m, 1H), 1.94(s, 3H), 1.73(m, 2H), hydrochloride 1.05(m, 3H) 312N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.04(m, 1H), 6.96(t, 1H),fluorophenylamino)-6- 6.75(m, 1H), 6.17(d, 1H), 4.51-4.43(m, 1H),3.92-3.40(m, propylpyrimidin-4- 4H), 2.60(m, 2H), 2.37(m, 1H), 2.10(m,1H), 1.95(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.75(q, 2H), 1.03(t, 3H)hydrochloride 313 (R)-N-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.91(s,1H), 7.54(d, 1H), nitrophenyl)-4-(2- 7.44(d, 1H), 5.83(brs, 1H),4.56-3.44(m, 3H), 2.62(dd, methylpyrrolidin-1-yl)-6- 2H), 2.26-2.03(m,3H), 1.88-1.79(m, 3H), 1.31(brs, 3H), propylpyrimidin-2-amine 1.02(t,3H) 314 (R)-4-(2-methylpyrrolidin-1- ¹H-NMR(400 MHz, CDCl₃) δ 8.57(s,1H), 7.80(s, 1H), yl)-N-[3-(methylthio)phenyl]- 7.34(dd, 1H), 7.20(dd,1H), 6.89(d, 1H), 5.70(brs, 1H), 6-propylpyrimidin-2-ylamine4.56-3.37(m, 3H), 2.53(dd, 2H), 2.48(s, 3H), 2.10- 2.04(m, 3H),1.82-1.73(m, 3H), 1.28(d, 3H), 0.99(t, 3H) 315 (R)-N-[4-(2- ¹H-NMR(400MHz, CDCl₃) δ 9.16(brs, 1H), 8.96(brs, 1H), methylpyrrolidin-1-yl)-6-8.02(s, 1H), 7.44(d, 1H), 7.13-7.11(m, 1H), 6.41(s, 1H),propylpyrimidin-2-yl]-1H- 5.46(s, 1H), 4.56-3.29(m, 3H), 2.39(dd, 2H),2.10- indol-6-amine 2.04(m, 3H), 1.72-1.66(m, 3H), 1.21(brs, 3H),0.93(t, 3H)

TABLE 1-33 Example Compound NMR Spectrum 316(R)-4-(2-methylpyrrolidin-1- ¹H-NMR(400 MHz, CDCl₃) δ 9.03(brs, 1H),8.48(s, 1H), yl)-6-propyl-N-[3- 7.51(d, 1H), 7.38(dd, 1H), 7.26(d, 1H),5.75(s, 1H), 4.48- (trifluoromethyl)phenyl]pyrimidin- 3.43(m, 3H),2.55(dd, 2H), 2.18-2.04(m, 3H), 1.84- 2-amine 1.74(m, 3H), 1.28(d, 3H),1.00(t, 3H) 317 (R)-4-methyl-7-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.20(s,1H), 7.69(brs, 1H), methylpyrrolidin-1-yl)-6- 7.46(d, 1H), 7.21(dd, 1H),6.11(s, 1H), 5.77(s, 1H), 4.14- propylpyrimidin-2-ylamino]- 3.32(m, 3H),2.50(dd, 2H), 2.39(s, 3H), 2.12-2.03(m, 2H-chromen-2-one 3H),1.79-1.71(m, 3H), 1.30(brs, 3H), 1.00(t, 3H) 318 (R)-N-(3-chloro-4-¹H-NMR(400 MHz, CDCl₃) δ 8.78(brs, 1H), 8.06(s, 1H), methylphenyl)-4-(2-7.23(d, 1H), 7.11(d, 1H), 5.70(s, 1H), 4.52-3.35(m, 3H),methylpyrrolidin-1-yl)-6- 2.53(dd, 2H), 2.31(s, 3H), 2.12-2.03(m, 3H),1.81- propylpyrimidin-2-amine 1.75(m, 3H), 1.30(brs, 3H), 1.00(t, 3H)319 (R)-4-(2-methylpyrrolidin-1- ¹H-NMR(400 MHz, CDCl₃) δ 9.23(dd, 1H),7.85(dd, 1H), yl)-N-(3-nitrophenyl)-6- 7.58(dd, 1H), 7.41(dd, 1H),5.78(s, 1H), 4.67-3.40(m, propylpyrimidin-2-ylamine 3H), 2.56(dd, 2H),2.12-2.03(m, 3H), 1.85-1.75(m, 3H), 1.32(brs, 3H), 1.01(t, 3H) 320(R)-N-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.08(d, 1H), 7.61-7.57(m,nitrophenyl)-4-(2- 1H), 7.22(dd, 1H), 5.81(s, 1H), 4.63-3.44(m, 3H),methylpyrrolidin-1-yl)-6- 2.60(dd, 2H), 2.22-2.08(m, 3H), 1.88-1.78(m,3H), propylpyrimidin-2-amine 1.32(brs, 3H), 1.02(t, 3H) 321(R)-N-(4-methyl-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.39(brs, 1H), 8.99(d, 1H),nitrophenyl)-4-(2- 7.43(dd, 1H), 7.23(d, 1H), 5.77(s, 1H), 4.60-3.38(m,3H), methylpyrrolidin-1-yl)-6- 2.56(dd, 2H), 2.55(s, 3H), 2.17-2.03(m,3H), 1.85- propylpyrimidin-2-amine 1.77(m, 3H), 1.30(brs, 3H), 1.01(t,3H) 322 (R)-N-[4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 9.02(brs, 1H),8.42(dd, 1H), (trifluoromethyl)phenyl]-4- 7.53-7.50(m, 1H), 7.11(dd,1H), 5.75(s, 1H), 4.47- (2-methylpyrrolidin-1-yl)-6- 3.34(m, 3H),2.55(dd, 2H), 2.55(s, 3H), 2.17-2.03(m, propylpyrimidin-2-ylamine 3H),1.83-1.76(m, 3H), 1.26(d, 3H), 1.00(t, 3H) 323 (R)-N¹-[4-(2- ¹H-NMR(400MHz, CDCl₃) δ 8.72(brs, 1H), 8.14(s, 1H), methylpyrrolidin-1-yl)-6-7.30-7.27(m, 1H), 6.72(d, 1H), 5.68(s, 1H), 4.33-3.38(m,propylpyrimidin-2-yl]-3- 3H), 4.09(s, 2H), 2.52(dd, 2H), 2.17-2.03(m,3H), 1.82- (trifluoromethyl)benzene- 1.72(m, 3H), 1.23(d, 3H), 0.99(t,3H) 1,4-diamine 324 (R)-benzyl 2-methoxy-5-[4- ¹H-NMR(400 MHz, CDCl₃) δ8.32(brs, 1H), 7.46-7.26(m, (2-methylpyrrolidin-1-yl)-6- 6H), 6.78(d,1H), 5.65(s, 1H), 5.19(s, 2H), 3.81(s, 3H), propylpyrimidin-2-4.44-3.34(m, 3H), 2.46(dd, 2H), 2.10-1.95(m, 3H), 1.76-ylamino]phenylcarbamate 1.68(m, 3H), 1.21(d, 3H), 0.98(t, 3H) 325(R)-2-fluoro-5-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, 1H), 7.60(brs,1H), methylpyrrolidin-1-yl)-6- 7.12(dd, 1H), 5.77(s, 1H), 4.45-3.36(m,3H), 2.54(dd, propylpyrimidin-2- 2H), 2.18-2.03(m, 3H), 1.83-1.73(m,3H), 1.31(brs, 3H), ylamino]benzonitrile 1.00(t, 3H)

TABLE 1-34 Example Compound NMR Spectrum 326 (R)-2-methyl-5-[4-(2-¹H-NMR(400 MHz, CDCl₃) δ 8.91(brs, 1H), 8.37(brs, 1H),methylpyrrolidin-1-yl)-6- 7.48(d, 1H), 7.21(d, 1H), 5.75(s, 1H),4.45-3.41(m, 3H), propylpyrimidin-2- 2.54(dd, 2H), 2.49(s, 3H),2.18-2.03(m, 3H), 1.83- ylamino]benzonitrile 1.75(m, 3H), 1.32(brs, 3H),1.00(t, 3H) 327 (R)-2-amino-5-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.12(brs,1H), 7.31(d, 1H), methylpyrrolidin-1-yl)-6- 7.16(brs, 1H), 6.69(d, 1H),4.20(s, 2H), 4.45-3.54(m, propylpyrimidin-2- 3H), 2.45(dd, 2H),2.09-2.01(m, 3H), 1.76-1.66(m, 3H), ylamino]benzonitrile 1.26(d, 3H),0.98(t, 3H) 328 (R)-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 8.97(s, 1H),8.87(brs, 1H), methylpyrrolidin-1-yl)-6- 7.29(dd, 1H), 6.73(d, 1H),6.23(s, 2H), 5.71(s, 1H), 4.63- propylpyrimidin-2-yl]-3- 3.33(m, 3H),2.53(dd, 2H), 2.09-2.01(m, 3H), 1.82- nitrobenzene-1,4-diamine 1.73(m,3H), 1.28(brs, 3H), 0.99(t, 3H) 329 (R)-1-{6-[4-(2- ¹H-NMR(400 MHz,CDCl₃) δ 8.65(brs, 1H), 7.44(brs, 1H), methylpyrrolidin-1-yl)-6- 7.07(d,1H), 5.68(s, 1H), 4.04(dd, 2H), 4.63-3.33(m, 3H), propylpyrimidin-2-3.13(dd, 2H), 2.50(dd, 2H), 2.20(s, 3H), 2.10-2.01(m, ylamino]indolin-1-3H), 1.79-1.73(m, 3H), 1.22(d, 3H), 0.99(t, 3H) yl}ethanone 330(R)-N-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.69(s, 1H), 7.04(d, 1H),methylphenyl)-4-(2- 6.84(dd, 1H), 6.68(brs, 1H), 5.71(s, 1H),4.46-3.27(m, methylpyrrolidin-1-yl)-6- 3H), 2.46(dd, 2H), 2.28(s, 3H),2.20-2.03(m, 3H), 1.75- propylpyrimidin-2-amine 1.67(m, 3H), 1.28(brs,3H), 0.99(t, 3H) 331 (R)-4-methoxy-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ7.18(s, 1H), 6.96(dd, 1H), methylpyrrolidin-1-yl)-6- 6.71(d, 1H),5.64(s, 1H), 4.56-3.33(m, 3H), 3.82(s, 3H), propylpyrimidin-2- 3.76(s,2H), 2.46(dd, 2H), 2.09-1.99(m, 3H), 1.77- yl]benzene-1,3-diamine1.66(m, 3H), 1.26(d, 3H), 0.98(t, 3H) 332 (R)-4-chloro-N¹-[4-(2-¹H-NMR(400 MHz, CDCl₃) δ 7.37(s, 1H), 7.10(d, 1H),methylpyrrolidin-1-yl)-6- 6.90(dd, 1H), 5.68(s, 1H), 4.56-3.33(m, 3H),3.96(s, 2H), propylpyrimidin-2- 2.45(dd, 2H), 2.07-2.00(m, 3H),1.76-1.66(m, 3H), yl]benzene-1,3-diamine 1.26(d, 3H), 0.99(t, 3H) 333(R)-4-fluoro-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 7.31(d, 1H), 6.97(s,1H), methylpyrrolidin-1-yl)-6- 6.87(d, 2H), 5.67(s, 1H), 4.56-3.33(m,3H), 3.67(s, 2H), propylpyrimidin-2- 2.45(dd, 2H), 2.12-1.98(m, 3H),1.75-1.68(m, 3H), yl]benzene-1,3-diamine 1.26(d, 3H), 0.98(t, 3H) 334(R)-4-methyl-N¹-[4-(2- ¹H-NMR(400 MHz, CDCl₃) δ 9.56(s, 1H), 7.08(d,1H), methylpyrrolidin-1-yl)-6- 7.02(s, 1H), 6.96(d, 3H), 5.66(s, 1H),4.55-3.36(m, 5H), propylpyrimidin-2- 2.56(dd, 2H), 2.15-2.07(m, 2H),2.12(s, 3H), 1.85- yl]benzene-1,3-diamine 1.76(m, 2H), 1.29(brs, 3H),1.00(t, 3H) 335 (S)-3-{4-[3-(2- ¹H-NMR(400 MHz, CD₃OD) δ 7.81-7.70(m,2H), 7.49(d, hydroxyethylamino)pyrrolidin- 1H), 7.30(d, 1H), 6.30(s,1H), 4.21-3.77(m, 9H), 2.69- 1-yl]-6-propylpyrimidin-2- 2.30(m, 4H),1.82(brs, 2H), 1.05(t, 3H) ylamino}benzonitrile dihydrochloride

TABLE 1-35 Example Compound NMR Spectrum 336 (S)-5-{4-butyl-6-[2-¹H-NMR(400 MHz, CD₃OD) δ 7.99(d, 1H), 7.70(d, 1H),(hydroxymethyl)pyrrolidin-1- 7.44(d, 1H), 6.31(d, 1H), 4.28(d, 1H),3.84-3.56(m, 4H), yl]pyrimidin-2-ylamino}-2- 2.66(dd, 2H), 2.51(s, 3H),2.12-2.02(m, 4H), 1.76- methylbenzonitrile 1.68(m, 2H), 1.48-1.43(m,2H), 1.03(t, 3H) hydrochloride 337 (S)-N-{1-[2-(4-amino-3- ¹H-NMR(400MHz, CD₃OD) δ 8.86(brs, 1H), 7.42(d, 1H), nitrophenylamino)-6- 6.90(d,1H), 5.83(s, 1H), 4.48(s, 1H), 3.78-3.40(m, 4H), butylpyrimidin-4-2.49(dd, 2H), 2.28-2.23(m, 1H), 2.04-1.99(m, 1H),yl]pyrrolidin-3-yl}acetamide 1.95(s, 3H), 1.71-1.64(m, 2H), 1.45-1.35(m,2H), 0.98(t, 3H) 338 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CDCl₃) δ9.06(brs, 1H), 7.34(d, 1H), (methylamino)pyrrolidin-1- 6.90(d, 1H),5.85(s, 1H), 3.96-3.44(m, 5H), 2.64(s, 3H), yl]pyrimidin-2-yl}-3-2.49(dd, 2H), 2.39(brs, 1H), 2.08(brs, 1H), 1.71-1.64(m,nitrobenzene-1,4-diamine 2H), 1.44-1.36(m, 2H), 0.96(t, 3H) 339(S)-3-(4-{3-[(1H-pyrrol-2- ¹H-NMR(400 MHz, CD₃OD) δ 10.59-10.51(m, 1H),yl)methylamino]pyrrolidin-1- 8.12(s, 1H), 7.83(d, 1H), 7.60-7.56(m, 2H),6.87-6.83(m, yl}-6-propylpyrimidin-2- 1H), 6.36-6.30(m, 2H),6.16-6.12(m, 1H), 4.36-4.33(m, ylamino)benzonitrile 2H), 4.12-3.75(m,5H), 2.71-2.58(m, 3H), 2.41-2.30(m, dihydrochloride 1H), 1.83-1.77(m,2H), 1.06(dd, 3H) 340 (S)-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 10.71(s,1H), 8.96(d, 1H), (methoxymethyl)pyrrolidin- 7.38(s, 1H), 6.85(s, 1H),6.15-6.13(m, 2H), 5.89(d, 1H), 1-yl]-6-propylpyrimidin-2-yl}-4.68-3.43(m, 5H), 3.31(d, 3H), 2.62(brs, 2H), 2.33-3-nitrobenzene-1,4-diamine 2.05(m, 4H), 1.88-1.84(m, 2H), 1.00(m, 3H)hydrochloride 341 (S)-{1-[2-(4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ13.50(s, 1H), 13.18(s, 1H), nitrophenylamino)-6- 11.25(s, 1H), 11.04(s,1H), 9.05(m, 1H), 8.97(m, 1H), propylpyrimidin-4- 7.63(m, 2H), 7.26(m,2H), 6.34(s, 1H), 5.84(s, 1H), yl]pyrrolidin-2-yl}methanol 4.62(m, 1H),4.20(m, 1H), 3.83(m, 2H), 3.81(m, 3H), hydrochloride 3.76(m, 3H),3.47(m, 2H), 2.65(m, 3H), 2.31(m, 3H), 2.13(m, 4H), 1.86(m, 4H), 1.01(m,6H) 342 (S)-N¹-[4-(3- ¹H-NMR(400MHz, CD₃OD) δ 7.97(d, 1H), 7.75(d, 1H),aminopyrrolidin-1-yl)-6- 7.30(d, 1H), 6.37(s, 1H), 4.17-3.75(m, 5H),2.71(t, 2H), propylpyrimidin-2-yl]-5- 2.58(m, 1H), 2.33(m, 1H), 1.82(m,2H), 1.06(t, 3H) (trifluoromethyl)benzene- 1,3-diamine dihydrochloride343 (S)-N¹-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 7.63(br, 1H), 7.60(s, 1H),aminopyrrolidin-1-yl)-6- 7.38(m, 1H), 6.31(d, 1H), 4.15-3.75(m, 5H),2.68(t, 2H), propylpyrimidin-2-yl]-3- 2.53(m, 1H), 2.43(d, 3H), 2.29(m,1H), 1.82(m, 2H), methylbenzene-1,4-diamine 1.07(t, 3H) dihydrochloride344 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.59(d, 1H),7.75-7.64(m, yl)-N-(4-chloro-3- 2H), 7.41(d, 1H), 6.57(d, 1H),4.11-3.78(m, 5H), nitrophenyl)-6- 2.72(m, 2H), 2.65(m, 1H), 2.04(m, 1H),1.78(m, 2H), propylpyrimidin-2-amine 1.06(m, 3H) dihydrochloride 345(S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 7.51(d, 1H),7.33(m, 2H), yl)-N-[3-(methylthio)phenyl]- 7.01(m, 1H), 6.28(brs, 1H),4.15-3.75(m, 5H), 2.67(m, 6-propylpyrimidin-2-amine 2H), 2.56(m, 1H),2.50(s, 3H), 2.24(m, 1H), 1.79(m, 2H), dihydrochloride 1.29(m, 3H)

TABLE 1-36 Example Compound NMR Spectrum 346(S)-N-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CD₃OD) δ 7.67(d, 1H),7.56(d, 1H), 1-yl)-6-propylpyrimidin-2-yl]- 7.28(s, 2H), 7.05(d, 1H),6.17(d, 1H), 4.14-3.71(m, 5H), 1H-indol-6-amine 2.62(m, 2H), 2.57(m,1H), 2.29(m, 1H), 1.78(m, 2H), dihydrochloride 1.04(t, 3H) 347(S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.20-8.05(d, 1H),7.81- yl)-6-propyl-N-[3- 7.30(dd, 1H), 7.62(m, 1H), 7.50(m, 1H), 6.34(d,1H), (trifluoromethyl)phenyl]pyrimidin- 4.17-3.74(m, 5H), 2.70(m, 2H),2.57(m, 1H), 2.25(m, 2-amine dihydrochloride 1H), 1.83(m, 2H), 1.06(t,3H) 348 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ7.77-7.67(d, 1H), 7.29(d, yl)-N-(5-chloro-2- 1H), 7.21(m, 1H), 6.28(d,1H), 4.11-3.70(m, 5H), 2.67(m, methylphenyl)-6- 2H), 2.55(m, 1H),2.30(d, 3H), 2.20(m, 1H), 1.79(m, 2H), propylpyrimidin-2-amine 1.05(t,3H) dihydrochloride 349 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz,CD₃OD) δ 7.78-7.71(d, 1H), 7.37- yl)-N-(3-chloro-4- 7.30(m, 2H), 6.28(s,1H), 4.08-3.81(m, 5H), 2.66(m, 2H), methylphenyl)-6- 2.52(m, 1H),2.35(s, 3H), 2.20(m, 1H), 1.80(m, 2H), propylpyrimidin-2-amine 1.05(t,3H) dihydrochloride 350 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz,CD₃OD) δ 8.94(d, 1H), 8.05(m, 1H), yl)-N-(3-nitrophenyl)-6- 7.82(m, 1H),7.64(m, 1H), 6.60(d, 1H), 4.16-3.76(m, 5H), propylpyrimidin-2-amine2.71(m, 2H), 2.55(m, 1H), 2.30(m, 1H), 1.84(m, 2H), dihydrochloride1.07(t, 3H) 351 (S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ8.64(d, 1H), 7.64(m, 1H), yl)-N-(4-methyl-3- 7.47(m, 1H), 6.64(d, 1H),4.16-3.71(m, 5H), 2.70(m, 2H), nitrophenyl)-6- 2.56(s, 3H), 2.54(m, 1H),2.31(m, 1H), 1.81(m, 2H), propylpyrimidin-2-amine 1.06(t, 3H)dihydrochloride 352 (S)-N¹-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 8.18(d, 1H),7.92-7.85(dd, aminopyrrolidin-1-yl)-6- 1H), 7.52(m, 1H), 6.35(s, 1H),6.78-4.18(m, 5H), 2.68(m, propylpyrimidin-2-yl]-3- 2H), 2.58(m, 1H),2.35(m, 1H), 1.82(m, 2H), 1.05(t, 3H) (trifluoromethyl)benzene-1,4-diamine dihydrochloride 353 (S)-5-[4-(3-aminopyrrolidin- ¹H-NMR(400MHz, CD₃OD) δ 8.07(d, 1H), 7.87(m, 1H), 1-yl)-6-propylpyrimidin-2-7.43(t, 1H), 6.33(s, 1H), 4.14-3.84(m, 5H), 2.69(m, 2H), ylamino]-2-2.56(m, 1H), 2.23(m, 1H), 1.80(m, 2H), 1.06(t, 3H) fluorobenzonitriledihydrochloride 354 (S)-5-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CD₃OD)δ 8.02(d, H), 7.68(d, 1H), 1-yl)-6-propylpyrimidin-2- 7.45(d, 1H),6.31(s, 1H), 4.08-3.82(m, 5H), 2.68(m, 2H), ylamino]-2- 2.58(m, 1H),2.52(s, 3H), 2.28(m, 1H), 1.80(m, 2H), methylbenzonitrile 1.06(t, 3H)dihydrochloride 355 (S)-2-amino-5-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ7.64(d, 1H), 7.45(m, 1H), aminopyrrolidin-1-yl)-6- 6.94(m, 1H), 6.25(s,1H), 4.13-3.70(m, 5H), 2.65(m, 2H), propylpyrimidin-2- 2.55(m, 1H),2.28(m, 1H), 1.78(m, 2H), 1.05(t, 3H) ylamino]benzonitriledihydrochloride

TABLE 1-37 Example Compound NMR Spectrum 356 (S)-benzyl 5-[4-(3-¹H-NMR(400 MHz, CD₃OD) δ 8.34(d, 1H), 7.44-7.31(m,aminopyrrolidin-1-yl)-6- 5H), 7.09-7.00(dd, 2H), 6.21(d, 1H), 5.20(d,2H), 4.01- propylpyrimidin-2-ylamino]- 3.72(m, 5H), 3.80(s, 3H), 2.64(m,2H), 2.62(m, 1H), 2-methoxyphenylcarbamate 2.54-2.29(m, 1H), 1.78(m,2H), 1.04(t, 3H) dihydrochloride 357 (S)-4-(3-aminopyrrolidin-1-¹H-NMR(400 MHz, CD₃OD) δ 8.12(d, 1H), 7.85(m, 1H), yl)-N-[4-fluoro-3-7.41(m, 1H), 6.30(s, 1H), 4.09-3.88(m, 5H), 2.71(m, 2H),(trifluoromethyl)phenyl]-6- 2.64(m, 1H), 2.30(m, 1H), 1.82(m, 2H),1.07(m, 3H) propylpyrimidin-2-amine dihydrochloride 358(S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.81-8.68(m, 1H),7.83(m, yl)-N-(4-fluoro-3- 1H), 7.49(m, 1H), 6.36(s, 1H), 4.18-3.76(m,5H), 2.70(m, nitrophenyl)-6- 2H), 2.58(m, 1H), 2.32(m, 1H), 1.82(m, 2H),1.06(t, 3H) propylpyrimidin-2-amine dihydrochloride 359 (S)-N¹-[4-(3-¹H-NMR(400 MHz, CD₃OD) δ 8.54(m, 1H), 7.43(m, 1H),aminopyrrolidin-1-yl)-6- 7.02(m, 1H), 6.25(d, 1H), 4.15-3.71(m, 5H),2.66(m, 2H), propylpyrimidin-2-yl]-3- 2.57(m, 1H), 2.30(m, 1H), 1.79(m,2H), 1.05(t, 3H) nitrobenzene-1,4-diamine dihydrochloride 360(S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 8.34-8.30(d, 2H),7.78(s, yl)-N-[3,5- 1H), 6.40(s, 1H), 4.16-3.77(m, 5H), 2.73(t, 2H),2.54(m, bis(trifluoromethyl)phenyl]- 1H), 2.26(m, 1H), 1.82(m, 2H),0.90(t, 3H) 6-propylpyrimidin-2-amine dihydrochloride 361(S)-4-(3-aminopyrrolidin-1- ¹H-NMR(400 MHz, CD₃OD) δ 6.81-6.78(m, 2H),6.35(s, yl)-N-(3,5- 1H), 6.28(s, 1H), 4.15-3.99(m, 4H), 3.85(s, 6H),3.84- dimethoxyphenyl)-6- 3.79(m, 1H), 2.66(t, 2H), 2.59(m, 1H), 2.50(m,1H), propylpyrimidin-2-amine 1.81(m, 2H), 1.05(t, 3H) dihydrochloride362 (S)-3-amino-5-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ 6.53(s, 1H), 6.26(m,2H), aminopyrrolidin-1-yl)-6- 5.83(s, 1H), 3.82(br, 1H), 3.65(m, 2H),3.48(br, 1H), propylpyrimidin-2- 3.30(br, 1H), 2.46(m, 2H), 2.21(m, 1H),1.89(m, 1H), yl]amino}benzonitrile 1.71(m, 2H), 0.97(t, 3H) 363(S)-3-[4-(3-aminopyrrolidin- ¹H-NMR(400 MHz, CD₃OD) δ 8.76(s, 1H),7.62(m, 1H), 1-yl)-6-propylpyrimidin-2- 7.41(m, 2H), 5.86(s, 1H),3.88-3.77(br, 1H), 3.65(m, 2H), ylamino]benzenesulfonamide 3.53(br, 2H),2.48(m, 2H), 2.21(m, 1H), 1.87(m, 1H), 1.74(m, 2H), 0.98(t, 3H) 364(S)-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.73(br, 1H), 7.04(t, 1H),(methoxymethyl)pyrrolidin- 6.97(br, 1H), 6.63(br, 1H), 6.30(m, 1H),5.68(br, 1H), 1-yl]-6-propylpyrimidin-2- 4.63(br, 1H), 3.92(m, 3H),3.45(br, 1H), 3.39(s, 3H), yl}benzene-1,3-diamine 3.18(br, 1H), 3.14(m,1H), 2.45(t, 2H), 2.10-1.96(m, 4H), 1.68(m, 3H), 0.99(t, 3H) 365(S)-4-fluoro-N¹-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ 7.82(br, 1H), 6.97(br,1H), (methoxymethyl)pyrrolidin- 6.85(m, 1H), 6.51(br, 1H), 5.68(s, 1H),4.46(br, 1H), 1-yl]-6-propylpyrimidin-2- 3.89(br, 2H), 3.45(br, 1H),3.39(s, 3H), 3.34(m, 1H), yl}benzene-1,3-diamine 3.12(m, 1H), 2.45(t,2H), 2.09-1.98(m, 4H), 1.68(m, 3H), 0.97(t, 3H)

TABLE 1-38 Example Compound NMR Spectrum 366 (S)-N¹-{4-[2- ¹H-NMR(400MHz, CDCl3) δ 7.72(br, 1H), 6.90(m, 2H), (methoxymethyl)pyrrolidin-6.57(br, 1H), 5.67(s, 1H), 4.51(br, 1H), 3.93-3.78(br, 2H),1-yl]-6-propylpyrimidin-2-yl}- 3.45(br, 1H), 3.40(s, 3H), 3.22(m, 1H),3.13(m, 1H), 4-methylbenzene-1,3- 2.45(m, 2H), 2.11(s, 3H), 1.99(m, 4H),1.69(m, 3H), diamine 0.98(t, 3H) 367 (S)-4-methoxy-N¹-{4-[2- ¹H-NMR(400MHz, CDCl₃) δ 7.62(br, 1H), 7.00(br, 1H), (methoxymethyl)pyrrolidin-6.70(m, 2H), 5.66(s, 1H), 4.72(br, 1H), 3.92(br, 2H),1-yl]-6-propylpyrimidin-2- 3.81(s, 3H), 3.40(m, 1H), 3.39(s, 3H),3.29(m, 1H), yl}benzene-1,3-diamine 3.17(m, 1H), 2.44(t, 2H), 2.02(m,4H), 1.71(m, 2H), 0.97(t, 3H) 368 (S)-N-{4-[2- ¹H-NMR(400 MHz, CDCl₃) δ7.40(br, 1H), 6.99(m, 1H), (methoxymethyl)pyrrolidin- 6.78(m, 1H),6.68(s, 1H), 4.40(br, 1H), 3.75(br, 1H), 1-yl]-6-propylpyrimidin-2-3.59(t, 2H), 3.53(br, 1H), 3.38(s, 3H), 3.36(m, 1H), yl}indolin-6-amine3.26(t, 1H), 2.99(t, 2H), 2.46(t, 2H), 2.09-1.95(m, 4H), 1.72(m, 2H),0.96(t, 3H) 369 (S)-N¹-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 7.17(s, 1H),6.94(s, 1H), aminopyrrolidin-1-yl)-6- 6.81(br, 1H), 5.65(s, 1H), 3.71(m,2H), 3.56(br, 1H), propylpyrimidin-2-yl]-4- 2.45(m, 2H), 2.19(m, 1H),2.12(s, 3H), 1.81(m, 1H), methylbenzene-1,3-diamine 1.70(m, 2H),1.26(br, 2H), 0.97(t, 3H) 370 (S)-N¹-[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ7.90(m, 1H), 7.65(m, 1H), aminopyrrolidin-1-yl)-6- 7.41(t, 1H), 6.32(s,1H), 4.16-3.77(m, 5H), 2.69(m, 2H), propylpyrimidin-2-yl]-4- 2.57(m,1H), 2.51(m, 1H), 1.81(m, 2H), 1.00(t, 3H) fluorobenzene-1,3-diaminedihydrochloride 371 (S)-3-amino-5-{[4-(3- ¹H-NMR(400 MHz, CD₃OD) δ7.85(d, 1H), 7.78(s, 1H), aminopyrrolidin-1-yl)-6- 7.28(m, 1H), 6.36(s,1H), 4.17-3.76(m, 5H), 2.70(m, 2H), propylpyrimidin-2- 2.60(m, 1H),2.33(m, 1H), 1.82(m, 2H), 1.06(t, 3H) yl]amino}benzonitriledihydrochloride 372 (S)-N-(4-chloro-3- ¹H-NMR(400 MHz, CDCl₃) δ9.05(brs, 1H), 7.37(d, 1H), nitrophenyl)-4-[3- 7.30(br, 1H), 7.15(br,1H), 5.75(s, 1H), 3.86-3.30(m, 5H), (cyclopropylmethylamino)pyrrol-2.55(d, 2H), 2.47(t, 2H), 2.23(m, 1H), 1.90(br, 1H),idin-1-yl]-6-propylpyrimidin-2-amine 1.72(m, 3H), 1.00(t, 4H), 0.55(d,2H), 0.15(m, 2H) 373 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 9.16(brs, 1H),7.40(br, 1H), (cyclopropylmethylamino)pyrrolidin- 7.17(br, 1H), 7.12(t,2H), 5.74(s, 1H), 3.90-3.15(m, 5H), 1-yl]-N-(4-fluoro-3- 2.56(d, 2H),2.47(t, 2H), 2.23(m, 1H), 1.90(br, 1H), nitrophenyl)-6- 1.74(m, 3H),0.97(t, 4H), 0.51(d, 2H), 0.16(d, 2H) propylpyrimidin-2-amine 374(S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 9.06(brs, 1H), 7.30(m, 1H),(cyclopropylmethylamino)pyrrol- 7.17(d, 1H), 7.10(br, 1H), 5.72(s, 1H),3.91-3.40(m, 5H), idin-1-yl]-N-(4-methyl-3- 2.57(m, 2H), 2.54(s, 3H),2.47(t, 2H), 2.23(m, 1H), nitrophenyl)-6- 1.90(br, 1H), 1.75(m, 3H),0.98(t, 3H), 0.52(d, 2H), propylpyrimidin-2-amine 0.15(m, 2H) 375(S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 9.26(brs, 1H), 7.77(d, 1H),(cyclopropylmethylamino)pyrrol- 7.44(m, 1H), 7.37(m, 1H), 5.74(s, 1H),3.92-3.60(m, 5H), idin-1-yl]-N-(3- 2.64(m, 2H), 2.48(t, 2H), 2.29(m,1H), 2.02(m, 1H), nitrophenyl)-6- 1.72(m, 2H), 1.00(m, 4H), 0.56(m, 4H),0.22(m, 2H) propylpyrimidin-2-amine

TABLE 1-39 Example Compound NMR Spectrum 376 (S)-5-{4-[3- ¹H-NMR(400MHz, CDCl₃) δ 8.34(m, 1H), 7.56(m, 1H), (cyclopropylmethylamino)pyrrol-7.09(m, 2H), 5.73(s, 1H), 3.84-3.16(m, 5H), 2.60(m, 2H), idin-1-yl]-6-2.47(t, 2H), 2.22(m, 1H), 1.88(br, 1H), 1.70(m, 3H),propylpyrimidin-2-ylamino}- 0.99(m, 4H), 0.50(m, 2H), 0.15(m, 2H)2-fluorobenzonitrile 377 (S)-5-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.32(d,1H), 7.46(d, 1H), (cyclopropylmethylamino)pyrrol- 7.18(d, 1H), 7.02(br,1H), 5.71(s, 1H), 3.80-3.00(m, 5H), idin-1-yl]-6- 2.54(d, 2H),2.48-2.45(m, 5H), 2.21(m, 1H), 1.88(br, 1H), propylpyrimidin-2-ylamino}-1.74(m, 3H), 0.98(t, 4H), 0.54(m, 2H), 0.17(m, 2H) 2-methylbenzonitrile378 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 7.86(s, 1H), 7.28(d, 1H),(cyclopropylmethylamino)pyrrol- 7.17(t, 1H), 6.96(br, 1H), 6.84(d, 1H),5.69(s, 1H), 4.00- idin-1-yl]-N-[3- 3.20(m, 5H), 2.54(d, 2H), 2.49(s,3H), 2.44(m, 2H), (methylthio)phenyl]-6- 2.20(m, 1H), 1.86(br, 1H),1.73(m, 3H), 0.97(m, 4H), propylpyrimidin-2-amine 0.50(m, 2H), 0.15(m,2H) 379 (S)-4-[3- ¹H-NMR(400 MHz, CDCl₃) δ 8.54(s, 1H), 7.40(m, 1H),(cyclopropylmethylamino)pyrrol- 7.33(m, 1H), 7.18(m, 2H), 5.71(s, 1H),4.10-3.00(m, 5H), idin-1-yl]-6-propyl-N-[3- 2.53(m, 2H), 2.46(t, 2H),2.21(m, 1H), 1.88(br, 1H), (trifluoromethyl)phenyl]pyrim- 1.72(m, 3H),0.97(t, 4H), 0.50(m, 2H), 0.15(m, 2H) idin-2-amine 380(S)-N-(5-chloro-2- ¹H-NMR(400 MHz, CDCl₃) δ 8.64(s, 1H), 7.03(d, 1H),methylphenyl)-4-[3- 6.86(d, 1H), 6.70(brs, 1H), 5.71(s, 1H),3.84-3.15(m, (cyclopropylmethylamino)pyrrol- 5H), 2.55(m, 2H), 2.47(t,2H), 2.27(s, 3H), 2.23(m, 1H), idin-1-yl]-6- 1.87(br, 1H), 1.71(m, 3H),0.98(m, 4H), 0.50(m, 2H), propylpyrimidin-2-amine 0.15(m, 2H) 381(S)-N-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ 8.03(s, 1H), 7.27(br, 1H),methylphenyl)-4-[3- 7.18(m, 1H), 7.09(m, 1H), 5.68(s, 1H), 4.00-3.15(m,5H), (cyclopropylmethylamino)pyrrol- 2.55(m, 2H), 2.47(m, 2H), 2.31(s,3H), 2.23(m, 1H), idin-1-yl]-6- 1.91(br, 1H), 1.68(m, 3H), 0.98(m, 4H),0.52(m, 2H), propylpyrimidin-2-amine 0.15(m, 2H) 382 (S)-4-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.48(brs, 1H), 7.39(brs, 1H),(cyclopropylmethylamino)pyrrol- 7.06(m, 2H), 5.71(s, 1H), 4.00-3.00(m,5H), 2.53(m, 2H), idin-1-yl]-N-[4-fluoro-3- 2.46(m, 2H), 2.21(m, 1H),1.88(m, 1H), 1.72(m, 3H), (trifluoromethyl)phenyl]-6- 0.97(m, 4H),0.52(m, 2H), 0.14(m, 2H) propylpyrimidin-2-amine 383 (S)-N¹-{4-[3-¹H-NMR(400 MHz, CDCl₃) δ 7.16(s, 1H), 6.96(m, 2H),(cyclopropylmethylamino)pyrrol- 5.64(s, 1H), 3.71-3.31(m, 7H), 2.54(dd,2H), 2.46(m, idin-1-yl]-6- 2H), 2.19(m, 1H), 2.12(s, 3H), 1.87(br, 1H),1.71(m, 3H), propylpyrimidin-2-yl}-4- 0.98(t, 4H), 0.51(m, 2H), 0.14(m,2H) methylbenzene-1,3-diamine 384 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CDCl₃) δ7.17(s, 1H), 7.09-6.99(m, (cyclopropylmethylamino)pyrrol- 2H), 6.32(d,1H), 5.66(s, 1H), 3.59-3.41(m, 7H), 2.53(m, idin-1-yl]-6- 2H), 2.32(m,2H), 2.20(m, 1H), 1.87(br, 1H), 1.68(m, propylpyrimidin-2- 3H), 0.96(m,4H), 0.51(m, 2H), 0.14(m, 2H) yl}benzene-1,3-diamine 385 (S)-5-{4-[3-¹H-NMR(400 MHz, CDCl₃) δ 8.16(br, 1H), 7.85(br, 1H),(cyclopropylmethylamino)pyrrol- 7.42(t, 1H), 6.31(s, 1H), 4.12-3.74(m,5H), 3.05(m, 2H), idin-1-yl]-6- 2.69(t, 2H), 2.58(br, 1H), 2.35(br, 1H),1.80(m, 2H), propylpyrimidin-2-ylamino}- 1.14(m, 1H), 1.05(t, 3H),0.75(m, 2H), 0.48(m, 2H) 2-fluorobenzonitrile dihydrochloride

TABLE 1-40 Example Compound NMR Spectrum 386 (S)-4-[3- ¹H-NMR(400 MHz,CD₃OD) δ 8.77(d, 1H), 7.60(m, 1H), (cyclopropylmethylamino)pyrrol-7.46(d, 1H), 6.33(s, 1H), 4.24-3.93(m, 5H), 3.05(m, 2H),idin-1-yl]-N-(4-methyl-3- 2.70(t, 2H), 2.63(m, 1H), 2.57(s, 3H),2.37(br, 1H), nitrophenyl)-6- 1.79(m, 2H), 1.22(m, 1H), 1.18(t, 3H),0.76(m, 2H), propylpyrimidin-2-amine 0.46(m, 2H) dihydrochloride 3873-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.16(d, 1H), 7.85-7.78(m,(cyclopropylmethylamino)pyrrol- 1H), 7.59(m, 2H), 6.35(s, 1H),4.19-3.73(m, 5H), 3.07- idin-1-yl]-6- 3.00(m, 2H), 2.67(t, 2H),2.63-2.60(m, 2H), 1.79(m, 2H), propylpyrimidin-2- 1.22(m, 1H), 1.16(t,3H), 0.74(m, 2H), 0.48(m, 2H) ylamino}benzonitrile dihydrochloride 388(S)-{1-[6-ethyl-2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.45(t, 2H), 7.18(t, 2H),fluorophenylamino)pyrimidin- 6.28-6.11(m, 1H), 4.35-4.09(d, 1H),3.70-3.45(m, 4H), 4-yl]pyrrolidin-2- 2.60(q, 2H), 2.10(m, 4H), 1.27(t,3H) yl}methanol 389 (S)-N-{1-[6-ethyl-2-(4- ¹H-NMR(400 MHz, CD₃OD) δ7.42(m, 2H), 7.19(t, 2H), fluorophenylamino)pyrimidin- 6.14-6.10(m, 1H),4.50(m, 1H), 3.86-3.40(m, 4H), 4-yl]pyrrolidin-3- 2.60(m, 2H), 2.31(m,1H), 2.10(m, 1H), 1.95(s, 3H), yl}acetamide 1.27(t, 3H) 390(S)-4-ethyl-N-(4- ¹H-NMR(400 MHz, CD₃OD) δ 7.43(m, 2H), 7.19(t, 2H),fluorophenyl)-6-(2- 6.28-6.11(m, 1H), 4.44-4.21(d, 1H), 3.59-3.54(m,4H), methoxymethylpyrrolidin-1- 3.24(d, 3H), 2.61(q, 2H), 2.04(m, 4H),1.26(t, 3H) yl)pyrimidin-2-amine 391 4-ethyl-N-(4-fluorophenyl)-¹H-NMR(400 MHz, CD₃OD) δ 7.43(t, 2H), 7.16(t, 2H),6-(2-methylpyrrolidin-1- 6.13-6.07(m, 1H), 4.37-4.18(d, 1H),3.69-3.44(m, 2H), yl)pyrimidin-2-amine 3.35(s, 3H), 2.63(q, 2H), 2.14(m,3H), 1.82(m, 1H), 1.27(t, 3H) 392 (S)-4-ethyl-6-[3- ¹H-NMR(400 MHz,CD₃OD) δ 7.45(m, 2H), 7.19(m, 2H), (ethylamino)pyrrolidin-1-yl]- 6.14(s,1H), 3.87-3.58(m, 5H), 2.84(m, 2H), 2.63(m, 2H),N-(4-fluorophenyl)pyrimidin- 2.36(m, 1H), 2.06(m, 1H), 1.27-1.22(m, 6H)2-amine 393 (S)-3-[4-(3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(s, 1H), 7.58(m,1H), phenoxypyrrolidin-1-yl)-6- 7.38(brs, 1H), 7.20(m, 3H), 7.20(d, 1H),7.00(t, 1H), propylpyrimidin-2- 6.90(m, 2H), 5.77(s, 1H), 5.08(s, 1H),3.77(m, 4H), ylamino]benzonitrile 2.51(t, 2H), 2.40(m, 1H), 2.27(m, 1H),1.73(q, 2H), 0.98(t, 3H) 394 (S)-N-{1-[2-(3- ¹H-NMR(400 MHz, CD₃OD) δ8.80(s, 1H), 8.77(t, 1H), cyanophenylamino)-6- 8.58(d, 1H), 8.17(d, 1H),8.07(m, 1H), 7.82-7.75(m, 1H), propylpyrimidin-4- 7.59-7.51(m, 2H),6.32(d, 1H), 4.58-4.50(m, 1H), 3.99(m, yl]pyrrolidin-3-yl}-2-(pyridin-1H), 3.82(m, 3H), 3.78-3.56(m, 3H), 2.66(m, 2H), 3-yl)acetamide 2.39(m,1H), 2.14(m, 1H), 1.80(m, 2H), 1.06(t, 3H) dihydrochloride

TABLE 1-41 Example Compound NMR Spectrum 395 (S)-2-amino-N-{1-[2-(3-¹H-NMR(400 MHz, CDCl₃) δ 8.33(s, 1H), 7.61(m, 2H), cyanophenylamino)-6-7.34(t, 1H), 7.20(d, 1H), 5.75(s, 1H), 4.63(m, 1H), propylpyrimidin-4-3.81(m, 3H), 3.38(s, 4H), 2.51(t, 2H), 2.33(m, 1H),yl]pyrrolidin-3-yl}acetamide 2.05(m, 1H), 1.71(m, 2H), 0.98(t, 3H) 396(S)-3-(4-{3-[4- ¹H-NMR(400 MHz, CD₃OD) δ 8.38(s, 1H), 7.77(d, 1H),(dimethylamino)benzylami- 7.45(t, 1H), 7.34(m, 3H), 6.81(d, 2H), 6.06(s,1H), no]pyrrolidin-1-yl}-6- 4.21(s, 2H), 4.04(m, 2H), 3.81-3.64(m, 3H),2.96(s, 6H), propylpyrimidin-2- 2.56(t, 3H), 2.31(m, 1H), 1.77(q, 2H),1.00(t, 3H) ylamino)benzonitrile dihydrochloride 397(S)-2-fluoro-5-{4-[2- ¹H-NMR(400 MHz, CD₃OD) δ 8.08-8.01(d, 1H), 7.86(m,(hydroxymethyl)pyrrolidin-1- 1H), 7.41(m, 1H), 6.41-6.23(d, 1H),4.34-4.18(d, 1H), yl]-6-propylpyrimidin-2- 3.71-3.55(m, 4H), 2.63(t,2H), 2.11(m, 4H), 1.77(m, 2H), ylamino}benzonitrile 1.05(t, 3H)hydrochloride 398 (S)-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ8.58-8.38(d, 1H), 7.41(m, nitrophenylamino)-6- 1H), 7.03(m, 1H),6.34-7.17(d, 1H), 4.40-4.17(d, 1H), propylpyrimidin-4- 3.88-3.62(m, 4H),2.61(t, 2H), 2.25-2.01(m, 4H), 1.76(m, yl]pyrrolidin-2-yl}methanol 2H),1.04(t, 3H) hydrochloride 399 (S)-{1-[2-(3-amino-4- ¹H-NMR(400 MHz,CDCl₃) δ 7.32(s, 1H), 6.92(d, 1H), methylphenylamino)-6- 6.78(brs, NH),6.67(d, 1H), 5.69(s, 1H), 4.41(brs, 1H), propylpyrimidin-4- 3.80(m, 1H),3.70(brs, 1H), 3.59(m, 1H), 3.46(m, 1H), yl]pyrrolidin-2-yl}methanol3.30(m, 1H), 2.44(t, 2H), 2.11(s, 3H), 2.02(m, 3H), 1.85(m, 1H), 1.71(m,2H), 0.98(t, 3H) 400 (S)-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ7.43(d, 1H), 6.86(m, 2H), fluorophenylamino)-6- 6.63(brs, 1H), 5.70(s,1H), 4.38(s, 1H), 3.86(s, 1H), propylpyrimidin-4- 3.76(m, 1H), 3.58(m,1H), 3.45(m, 1H), 3.29(brs, 1H), yl]pyrrolidin-2-yl}methanol 2.45(t,3H), 2.01(m, 3H), 1.85(m, 1H), 1.70(m, 2H), 0.97(t, 3H) 401(S)-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CDCl₃) δ 7.52(s, 1H), 7.00(d, 1H),chlorophenylamino)-6- 6.68(m, 1H), 5.73(s, 1H), 4.43(m, 1H), 4.22(m,1H), propylpyrimidin-4- 3.82(m, 1H), 3.62(m, 1H), 3.49(m, 1H), 3.34(m,1H), yl]pyrrolidin-2-yl}methanol 2.49(t, 2H), 2.05(m, 2H), 1.63(m, 4H),0.98(t, 3H) 402 (S)-3-[4-(2-formylpyrrolidin- ¹H-NMR(400 MHz, CDCl₃) δ9.61(s, 1H), 8.12(s, 1H), 1-yl)-6-propylpyrimidin-2- 7.57(d, 1H),7.34(t, 1H), 7.24(t, 1H), 7.13(s, 1H), 5.84(s, ylamino]benzonitrile 1H),4.54(s, 1H), 3.62-3.52(m, 2H), 2.53(t, 2H), 2.22(s, 1H), 2.09(m, 3H),1.73(m, 2H), 0.99(t, 3H) 403 (S)-3-(4-{2- ¹H-NMR(400 MHz, CD₃OD) δ8.32(s, 1H), 7.83(d, 1H), [(methylamino)methyl]pyrrol- 7.41(t, 1H),7.22(d, 1H), 5.94(s, 1H), 4.30(brs, 1H), 3.56-idin-1-yl}-6-propylpyrimidin- 3.38(m, 2H), 2.86(s, 1H), 2.62(m, 1H),2.48(t, 2H), 2-ylamino)benzonitrile 2.40(s, 3H), 2.04(m, 4H), 1.74(m,2H), 0.99(t, 3H)

TABLE 1-42 Example Compound NMR Spectrum 404 (S)-3-(4-{2- ¹H-NMR(400MHz, CDCl₃) δ 8.75(s, 1H), 8.45(s, 1H), [(cyclobutylamino)methyl]pyrrol-7.87(s, 1H), 7.31(m, 1H), 7.19(d, 1H), 5.80(s, 1H), idin-1-yl}-6-4.52(s, 1H), 3.45-3.31(m, 2H), 2.92-2.81(m, 2H), 2.53(m,propylpyrimidin-2- 2H), 2.23-2.01(m, 7H), 1.75(m, 4H), 0.88(t, 3H)ylamino)benzonitrile 405 (S)-3-(4-{2-[(4- ¹H-NMR(400 MHz, CDCl₃) δ8.37(s, 1H), 7.64(s, 1H), fluorobenzylamino)methyl]pyrrol- 7.33-7.19(m,4H), 6.94(m, 2H), 5.75(s, 1H), 4.44(s, 1H), idin-1-yl}-6- 3.85(s, 2H),3.45-3.31(m, 2H), 2.87-2.76(m, 2H), 2.48(m, propylpyrimidin-2- 2H),2.02(m, 4H), 1.71(m, 2H), 0.98(t, 3H) ylamino)benzonitrile 406(S)-3-(4-propyl-6-{2- ¹H-NMR(400 MHz, CDCl₃) δ 9.44(s, 1H), 8.56(s, 1H),[(propylamino)methyl]pyrrol- 7.99(m, 1H), 7.30(m, 1H), 7.18(d, 1H),5.80(s, 1H), idin-1-yl}pyrimidin-2- 4.69(s, 1H), 3.48-3.32(m, 3H),3.02(m, 1H), 2.82(m, 2H), ylamino)benzonitrile 2.54(t, 2H), 2.16(m, 1H),1.98(m, 2H), 1.88-1.75(m, 5H), 0.98(t, 3H), 0.89(t, 3H) 407(S)-3-(4-{2-[(2- ¹H-NMR(400 MHz, CDCl₃) δ 9.11(s, 1H), 8.48(s, 1H),hydroxyethylamino)methyl]pyrrol- 7.89(d, 1H), 7.31(m, 1H), 7.17(d, 1H),5.78(s, 1H), idin-1-yl}-6- 4.30(m, 1H), 4.10(m, 1H), 3.92(m, 1H),3.45(m, 1H), propylpyrimidin-2- 3.37(m, 2H), 3.14-3.04(m, 2H), 2.92(m,1H), 2.55(t, 2H), ylamino)benzonitrile 2.23(m, 1H), 1.97(m, 2H),1.80-1.75(m, 3H), 1.01(t, 3H) 408 N-{1-[2-(3- ¹H-NMR(400 MHz, CD₃OD) δ8.14-8.02(d, 1H), 7.85(m, cyanophenylamino)-6- 1H), 7.58-7.52(m, 2H),6.29(d, 1H), 4.52(m, 1H), 3.95- propylpyrimidin-4- 3.48(m, 4H), 2.66(m,2H), 2.33(m, 1H), 2.10(m, 1H), yl]pyrrolidin-3-yl}acetamide 1.95(s, 3H),1.77(m, 2H), 1.05(m, 3H) hydrochloride 409 N-{1-[2-(3- ¹H-NMR(400 MHz,CD₃OD) δ 8.97(d, 1H), 8.03(m, 1H), nitrophenylamino)-6- 7.79(m, 1H),7.60(m, 1H), 6.27(m, 1H), 4.53(m, 1H), propylpyrimidin-4- 3.99-3.48(m,4H), 2.66(m, 2H), 2.33(m, 1H), 2.10(m, yl]pyrrolidin-3-yl}acetamide 1H),1.96(s, 3H), 1.78(m, 2H), 1.06(m, 3H) hydrochloride 410N-{1-[2-(4-chloro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.64-8.52(d, 1H), 7.71-nitrophenylamino)-6- 7.66(m, 2H), 6.32(d, 1H), 4.52(m, 1H), 4.10-3.62(m,4H), propylpyrimidin-4- 2.69(m, 2H), 2.34(m, 1H), 2.13(m, 1H), 1.99(s,3H), yl]pyrrolidin-3-yl}acetamide 1.77(m, 2H), 1.04(m, 3H) hydrochloride411 (R)-N¹-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 8.56(s, 1H), 7.41(m, 1H),methylpyrrolidin-1-yl)-6- 6.99(d, 1H), 6.21(m, 1H), 4.52-4.23(m, 2H),3.81-3.48(m, propylpyrimidin-2-yl]-3- 2H), 2.63(t, 2H), 2.15(m, 3H),1.74(m, 2H), 1.25(m, 3H), nitrobenzene-1,4-diamine 1.03(t, 3H)hydrochloride 412 (R)-N¹-[4-(2- ¹H-NMR(400 MHz, CD₃OD) δ 8.15-8.10(m,1H), 7.66- methylpyrrolidin-1-yl)-6- 7.65(m, 1H), 7.30-7.25(m, 1H),6.29-6.17(d, 1H), 4.45- propylpyrimidin-2-yl]-3- 4.24(m, 1H),3.78-3.47(m, 2H), 2.63(m, 2H), 2.21- (trifluoromethyl)benzene- 2.07(m,3H), 1.78(m, 3H), 1.27(m, 3H), 1.05(t, 3H) 1,4-diamine hydrochloride 413(S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.12-8.03(d, 1H), 7.65(m,(cyclopropylmethylamino)pyrrol- 1H), 7.44(d, 1H), 6.32(s, 1H), 4.14(m,2H), 3.94-3.75(m, idin-1-yl]-6- 3H), 3.06-3.00(m, 2H), 2.68(t, 2H),2.61(m, 1H), 2.52(s, propylpyrimidin-2-ylamino}- 3H), 2.38-2.36(m, 1H),1.82-1.76(m, 2H), 1.15(m, 1H), 2-methylbenzonitrile 1.05(t, 3H), 0.74(m,2H), 0.48(m, 2H) dihydrochloride

TABLE 1-43 Example Compound NMR Spectrum 414 (S)-2-methyl-5-{4-propyl-6-¹H-NMR(400 MHz, CD₃OD) δ 8.37(d, 1H), 7.64(d, 1H),[3-(propylamino)pyrrolidin- 7.26(d, 1H), 5.87(d, 1H), 4.00-3.30(m, 5H),2.90-2.60(m, 1-yl]pyrimidin-2- 2H), 2.48(t, 2H), 2.44(s, 3H),2.40-2.25(m, 1H), 2.05- ylamino}benzonitrile 1.90(m, 1H), 1.80-1.50(m,4H), 1.00-0.90(m, 6H) 415 (S)-2-methyl-5-(4-{3-[3- ¹H-NMR(400 MHz,CD₃OD) δ 8.36(s, 1H), 7.66(d, 1H), (methylthio)propylamino]pyrrol-7.26(d, 1H), 5.87(s, 1H), 3.90-3.30(m, 5H), 2.81(t, 2H), idin-1-yl}-6-2.57(t, 2H), 2.48(t, 2H), 2.45(s, 3H), 2.30-2.20(m, 1H),propylpyrimidin-2- 2.09(s, 3H), 2.00-1.90(m, 1H), 1.84(t, 2H), 1.75(q,2H), ylamino)benzonitrile 0.98(t, 3H) 416 (S)-5-(4-{3-[(1H-pyrrol-2-¹H-NMR(400 MHz, CD₃OD) δ 8.35(s, 1H), 7.66(dd, 1H),yl)methylamino]pyrrolidin-1- 7.26(d, 1H), 6.69(s, 1H), 6.10-6.00(m, 2H),5.84(s, 1H), yl}-6-propylpyrimidin-2- 3.86(s, 2H), 3.80-3.30(m, 5H),2.47(t, 2H), 2.45(s, 3H), ylamino)-2- 2.25-2.15(m, 1H), 2.00-1.90(m,1H), 1.72(q, 2H), 0.98(t, methylbenzonitrile 3H) 417 (S)-5-{4-[3-(4-¹H-NMR(400 MHz, CD₃OD) δ 8.36(s, 1H), 7.65(d, 1H),hydroxybenzylamino)pyrrol- 7.30-7.20(m, 3H), 6.77(d, 1H), 5.85(s, 1H),3.82(s, 2H), idin-1-yl]-6-propylpyrimidin- 3.80-3.30(m, 5H), 2.48(t,2H), 2.44(s, 3H), 2.30-2.20(m, 2-ylamino}-2- 1H), 2.00-1.90(m, 1H),1.72(q, 2H), 0.98(t, 3H) methylbenzonitrile 418 (S)-5-{4-[3- ¹H-NMR(400MHz, CD₃OD) δ 8.35(s, 1H), 7.66(d, 1H), (isopropylamino)pyrrolidin-7.25(d, 1H), 5.86(s, 1H), 4.00-3.35(m, 5H), 3.01(t, 1H),1-yl]-6-propylpyrimidin-2- 2.47(t, 2H), 2.44(s, 3H), 2.35-2.25(m, 1H),1.90-1.85(m, ylamino}-2- 1H), 1.73(q, 2H), 1.20-1.10(m, 6H), 0.98(t, 3H)methylbenzonitrile 419 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.33(s,1H), 7.67(d, 1H), (cyclobutylamino)pyrrolidin- 7.25(d, 1H), 5.84(s, 1H),3.90-3.30(m, 6H), 2.47(t, 2H), 1-yl]-6-propylpyrimidin-2- 2.44(s, 3H),2.30-2.15(m, 3H), 2.00-1.60(m, 7H), 0.98(t, ylamino}-2- 3H)methylbenzonitrile 420 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.36(s,1H), 7.64(d, 1H), (cyclopentylamino)pyrrolidin- 7.25(d, 1H), 5.85(s,1H), 4.00-3.35(m, 5H), 3.21(t, 1H), 1-yl]-6-propylpyrimidin-2- 2.47(t,2H), 2.44(s, 3H), 2.35-2.25(m, 1H), 2.05-1.80(m, ylamino}-2- 3H),1.80-1.50(m, 6H), 1.40-1.30(m, 2H), 0.99(t, 3H) methylbenzonitrile 421(S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.35(s, 1H), 7.63(d, 1H),(cyclohexylamino)pyrrolidin- 7.23(d, 1H), 5.83(s, 1H), 4.00-3.10(m, 5H),2.60(t, 1H), 1-yl]-6-propylpyrimidin-2- 2.46(t, 2H), 2.43(s, 3H),2.30-2.20(m, 1H), 2.00-1.60(m, ylamino}-2- 7H), 1.45-1.05(m, 6H),0.98(t, 3H) methylbenzonitrile 422 (S)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz,CD₃OD) δ 8.20-8.00(m, 1H), 7.70- (pentylamino)pyrrolidin-1- 7.61(m, 1H),7.45(d, 1H), 6.32(s, 1H), 4.20-3.60(m, 5H), yl]-6-propylpyrimidin-2-3.20-3.00(m, 2H), 2.68(t, 2H), 2.65-2.55(m, 1H), 2.52(s,ylamino}benzonitrile 3H), 2.40-2.25(m, 1H), 1.90-1.70(m, 4H),1.50-1.30(m, dihydrochloride 4H), 1.05(t, 3H), 1.00-0.90(m, 3H) 423(S)-2-methyl-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.08(d, 1H), 7.75-7.55(m,(neopentylamino)pyrrolidin- 1H), 7.50-7.40(m, 1H), 6.32(s, 1H),4.30-3.60(m, 5H), 1-yl]-6-propylpyrimidin-2- 3.10-2.90(m, 2H),2.80-2.60(m, 3H), 2.52(s, 3H), 2.50- ylamino}benzonitrile 2.30(m, 1H),1.80(q, 2H), 1.12(s, 9H), 1.05(t, 3H) dihydrochloride

TABLE 1-44 Example Compound NMR Spectrum 424 (S)-5-(4-{3-[(4,5-¹H-NMR(400 MHz, CD₃OD) δ 8.10-8.00(m, 1H), 7.73(d, dimethylfuran-2- 1H),7.45(d, 1H), 6.48(s, 1H), 6.31(s, 1H), 4.40-4.20(m,yl)methylamino]pyrrolidin-1- 2H), 4.20-3.60(m, 5H), 2.68(t, 2H),2.60-2.50(m, 1H), yl}-6-propylpyrimidin-2- 2.52(s, 3H), 2.40-2.30(m,1H), 2.25-2.15(m, 3H), 1.93(s, ylamino)-2- 3H), 1.80(q, 2H), 1.05(t, 3H)methylbenzonitrile dihydrochloride 425 (S)-N-{1-[2-(3-cyano-4-¹H-NMR(400 MHz, CD₃OD) δ 8.24(brs, 1H), 7.71(d, 1H),methylphenylamino)-6- 7.27(d, 1H), 5.89(s, 1H), 4.47(t, 1H),3.90-3.30(m, 4H), propylpyrimidin-4- 2.49(t, 2H), 2.44(s, 3H),2.30-2.15(m, 3H), 2.10-2.00(m, yl]pyrrolidin-3- 1H), 1.73(q, 2H),1.12(t, 3H), 0.98(t, 3H) yl}propionamide 426 (S)-N-{1-[2-(3-cyano-4-¹H-NMR(400 MHz, CD₃OD) δ 7.97(brs, 1H), 7.72(d, 1H),methylphenylamino)-6- 7.35-7.15(m, 6H), 5.92(s, 1H), 4.50-4.40(m, 1H),3.90- propylpyrimidin-4- 3.40(m, 6H), 2.50(t, 2H), 2.46(s, 3H),2.30-2.20(m, 1H), yl]pyrrolidin-3-yl}-2- 2.10-2.00(m, 1H), 1.73(q, 2H),0.99(t, 3H) phenylacetamide 427 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz,CD₃OD) δ 8.28(s, 1H), 7.69(dd, 1H), methylphenylamino)-6- 7.25(d, 1H),5.88(s, 1H), 4.51(t, 1H), 3.90-3.35(m, 4H), propylpyrimidin-4- 3.09(s,2H), 2.60-2.45(m, 6H), 2.44(s, 3H), 2.35-2.25(m, yl]pyrrolidin-3-yl}-2-1H), 2.10-2.00(m, 1H), 1.80-1.65(m, 2H), 1.60-1.50(m,(piperidin-1-yl)acetamide 4H), 1.50-1.40(m, 2H), 0.98(t, 3H) 428(S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.84(s, 1H),8.80-8.70(m, methylphenylamino)-6- 1H), 8.56(d, 1H), 8.10-8.00(m, 2H),7.70-7.60(m, 1H), propylpyrimidin-4- 7.43(t, 1H), 6.25(d, 1H),4.55-4.45(m, 1H), 4.10-3.50(m, yl]pyrrolidin-3-yl}-2-(pyridin- 6H),2.70-2.60(m, 2H), 2.51(d, 3H), 2.40-2.25(m, 1H), 3-yl)acetamide2.20-2.05(m, 1H), 1.80-1.65(m, 2H), 1.10-1.00(m, 3H) 429(S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.50-8.40(m, 2H),8.29(s, methylphenylamino)-6- 1H), 7.70(dd, 1H), 7.36(d, 2H), 7.26(d,1H), 5.87(s, 1H), propylpyrimidin-4- 4.48(t, 1H), 3.90-3.30(m, 6H),2.50-2.40(m, 5H), 2.30- yl]pyrrolidin-3-yl}-2-(pyridin- 2.20(m, 1H),2.10-2.00(m, 1H), 1.73(q, 2H), 0.98(t, 3H) 4-yl)acetamide 430(S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.24(brs, 1H), 7.72(d,1H), methylphenylamino)-6- 7.30-7.20(m, 2H), 7.00-6.90(m, 2H), 5.86(s,1H), 4.47(t, propylpyrimidin-4- 1H), 3.90-3.30(m, 6H), 2.48(t, 2H),2.44(s, 3H), 2.20(m, yl]pyrrolidin-3-yl}-2- 1H), 2.10-2.00(m, 1H),1.73(q, 2H), 0.98(t, 3H) (thiophen-2-yl)acetamide 431(S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.29(s, 1H), 7.70(dd,1H), methylphenylamino)-6- 5.88(s, 1H), 4.15(t, 1H), 3.90-3.30(m, 4H),3.02(s, 3H), propylpyrimidin-4- 2.49(t, 2H), 2.44(s, 3H), 2.35-2.25(m,1H), 2.10-2.00(m, yl]pyrrolidin-3- 1H), 1.73(q, 2H), 0.98(t, 3H)yl}methanesulfonamide 432 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD)δ 8.02(d, 1H), 7.70(d, 1H), methylphenylamino)-6- 7.44(d, 1H), 6.26(s,1H), 4.30-4.10(m, 1H), 4.00-3.40(m, propylpyrimidin-4- 4H), 3.03(s, 3H),2.65(t, 2H), 2.52(s, 3H), 2.45-2.30(m, yl]pyrrolidin-3- 1H),2.20-2.00(m, 1H), 1.77(q, 2H), 1.05(t, 3H) yl}methanesulfonamidehydrochloride

TABLE 1-45 Example Compound NMR Spectrum 433 (S)-1-(1-{2-[(3-cyano-4-¹H-NMR(400 MHz, CD₃OD) δ 8.00(d, 1H), 7.80-7.60(m,methylphenyl)amino]-6- 1H), 7.44(d, 1H), 6.24(d, 1H), 4.45-4.30(m, 1H),4.00- propylpyrimidin-4- 3.30(m, 4H), 3.20-3.00(m, 2H), 2.70-2.60(m,2H), 2.51(s, yl}pyrrolidin-3-yl)-3- 3H), 2.40-2.20(m, 1H), 2.15-2.00(m,1H), 1.90-1.70(m, ethylurea hydrochloride 2H), 1.20-1.00(m, 6H) 434(R)-3-(4-{3- ¹H-NMR(400 MHz, CD₃OD) δ 8.40(s, 1H), 7.81(d, 1H),[(diethylamino)methyl]pyrrol- 7.39(t, 1H), 7.22(d, 1H), 5.87(s, 1H),3.90-3.20(m, 4H), idin-1-yl}-6-propylpyrimidin- 2.80-2.50(m, 6H),2.48(t, 2H), 2.20-2.10(m, 1H), 1.80- 2-ylamino)benzonitrile 1.65(m, 3H),1.10(t, 6H), 0.98(t, 3H) 435 (S)-5-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ8.03(d, 1H), 7.64(brs, 1H), (isopropylamino)pyrrolidin- 7.45(d, 1H),6.32(s, 1H), 4.20-3.74(m, 5H), 3.56-3.51(m, 1-yl]-6-propylpyrimidin-2-1H), 2.67(dd, 2H), 2.60(brs, 1H), 2.36-2.31(m, 1H), 1.84- ylamino}-2-1.74(m, 2H), 1.42(dd, 6H), 1.05(t, 3H) methylbenzonitriledihydrochloride 436 (S)-N-{1-[6-butyl-2-(4- ¹H-NMR(400 MHz, CD₃OD) δ8.68-8.56(d, 1H), 7.60(t, methyl-3- 1H), 7.44(d, 1H), 6.24(d, 1H),4.49(m, 1H), 4.00-3.48(m, nitrophenylamino)pyrimidin- 4H), 2.68(m, 2H),2.56(s, 3H), 2.33(m, 1H), 2.11(m, 1H), 4-yl]pyrrolidin-3- 1.96(s, 3H),1.73(m, 2H), 1.45(m, 2H), 0.98(t, 3H) yl}acetamide hydrochloride 437(S)-N-{1-[6-butyl-2-(4- ¹H-NMR(400 MHz, CD₃OD) δ 8.78-8.66(d, 1H),7.79(m, fluoro-3- 1H), 7.47(t, 1H), 6.30-6.27(d, 1H), 4.52(m, 1H), 4.48-nitrophenylamino)pyrimidin- 3.48(m, 4H), 2.69(m, 2H), 2.36(m, 1H),2.10(m, 1H), 4-yl]pyrrolidin-3- 1.95(s, 3H), 1.73(s, 3H), 1.45(m, 2H),0.98(t, 3H) yl}acetamide hydrochloride 438 (S)-N-{1-[6-butyl-2-(4-¹H-NMR(400 MHz, CD₃OD) δ 8.65-8.54(d, 1H), 8.40- chloro-3- 8.37(m, 1H),7.72-7.65(m, 2H), 6.31-6.28(d, 1H), 4.51(m, nitrophenylamino)pyrimidin-1H), 3.96-3.48(m, 4H), 2.69(m, 2H), 2.32(m, 1H), 4-yl]pyrrolidin-3-2.13(m, 1H), 1.96(s, 3H), 1.72(m, 2H), 1.45(m, 2H), yl}acetamidehydrochloride 1.00(t, 3H) 439 (S)-N-{1-[2-(3-amino-5- ¹H-NMR(400 MHz,CD₃OD) δ 8.06-7.83(m, 2H), 7.36(d, cyanophenylamino)-6- 1H), 6.33(d,1H), 4.53-4.47(m, 1H), 4.00-3.49(m, 4H), butylpyrimidin-4- 2.70(m, 2H),2.40(m, 1H), 2.16(m, 1H), 1.97(s, 3H), yl]pyrrolidin-3-yl}acetamide1.73(m, 2H), 1.44(m, 2H), 1.02(t, 3H) hydrochloride 440(S)-N-(1-{2-[3-amino-5- ¹H-NMR(400 MHz, CD₃OD) δ 8.14-8.02(d, 1H),7.30(d, (trifluoromethyl)phenylamino]- 1H), 6.33(d, 1H), 4.53-4.47(m,1H), 3.97-3.49(m, 4H), 6-butylpyrimidin-4- 2.71(m, 2H), 2.31(m, 1H),2.15(m, 1H), 1.96(s, 3H), yl}pyrrolidin-3-yl)acetamide 1.74(m, 2H),1.47(m, 2H), 0.99(t, 3H) hydrochloride 441 (S)-N-(1-{2-[4-amino-3-¹H-NMR(400 MHz, CD₃OD) δ 7.74-7.65(d, 1H), 7.34(d,(trifluoromethyl)phenylamino]- 1H), 6.86(d, 1H), 6.13(d, 1H), 4.49(m,1H), 3.83-3.43(m, 6-butylpyrimidin-4- 4H), 2.63(m, 2H), 2.30(m, 1H),2.08(m, 1H), 1.94(s, 3H), yl}pyrrolidin-3-yl)acetamide 1.69(m 2H),1.45(m, 2H), 0.99(t, 3H) hydrochloride 442 (S)-N-(1-{6-butyl-2-[4-¹H-NMR(400 MHz, CD₃OD) δ 8.19-8.10(d, 1H), 7.76(m, fluoro-3- 1H),7.38(t, 1H), 6.27(d, 1H), 4.51(m, 1H), 3.89-3.48(m,(trifluoromethyl)phenylami- 4H), 2.68(m, 2H), 2.31(m, 1H), 2.11(m, 1H),1.95(s, 3H), no]pyrimidin-4-yl}pyrrolidin-3- 1.72(m, 2H), 1.45(m, 2H),1.00(t, 3H) yl)acetamide hydrochloride

TABLE 1-46 Example Compound NMR Spectrum 443 (S)-N-{1-[6-butyl-2-(3-¹H-NMR(400 MHz, CD₃OD) δ 8.09-7.99(d, 1H), 7.87(m, cyano-4- 1H), 7.41(t,1H), 6.24(d, 1H), 4.51-4.45(m, 1H), 3.89- fluorophenylamino)pyrimidin-3.48(m, 4H), 2.69(m, 2H), 2.28(m, 1H), 2.11(m, 1H), 4-yl]pyrrolidin-3-1.95(s, 3H), 1.72(m, 2H), 1.45(m, 2H), 1.00(t, 3H) yl}acetamidehydrochloride 444 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ7.03(m, 1H), 6.98(t, 1H), fluorophenylamino)-6- 6.74(m, 1H), 6.17(d,1H), 4.50-4.44(m, 1H), 2.63(m, 2H), butylpyrimidin-4- 2.33(m, 1H),2.09(m, 1H), 1.95(s, 3H), 1.67(m, 2H), yl]pyrrolidin-3-yl}acetamide1.43(m, 2H), 0.99(t, 3H) hydrochloride 445 (S)-N-{1-[2-(3-amino-4-¹H-NMR(400 MHz, CD₃OD) δ 7.18(d, 1H), 7.07(s, 1H), chlorophenylamino)-6-6.79(m, 1H), 6.16(d, 1H), 4.51-4.45(m, 1H), 3.93-3.47(m,butylpyrimidin-4- 4H), 2.64(m, 2H), 2.34(m, 1H), 2.10(m, 1H), 1.95(s,3H), yl]pyrrolidin-3-yl}acetamide 1.69(m, 2H), 1.45(m, 2H), 0.99(t, 3H)hydrochloride 446 (S)-N-{1-[2-(4-amino-3- ¹H-NMR(400 MHz, CD₃OD) δ7.59(d, 1H), 7.40(s, 1H), cyanophenylamino)-6- 6.84(m, 1H), 6.13(m, 1H),4.49(m, 1H), 3.84-3.44(m, butylpyrimidin-4- 4H), 2.63(m, 2H), 2.32(m,1H), 2.25(m, 1H), 1.94(s, 3H), yl]pyrrolidin-3-yl}acetamide 1.69(m, 2H),1.44(m, 2H), 0.99(m, 3H) hydrochloride 447 (S)-2-amino-5-{4-butyl-6-[3-¹H-NMR(400 MHz, CD₃OD) δ 7.65(s, 1H), 7.42(t, 1H),(methylamino)pyrrolidin-1- 6.94(d, 1H), 6.25(d, 1H), 4.04-3.73(m, 5H),2.78(d, 3H), yl]pyrimidin-2- 2.59(t, 2H), 2.49(m, 1H), 2.36(m, 1H),1.71(m, 2H), ylamino}benzonitrile 1.45(m, 2H), 1.00(t, 3H)dihydrochloride 448 (S)-4-butyl-N-(4-methyl-3- ¹H-NMR(400 MHz, CD₃OD) δ8.81-8.79(m, 1H), 7.56(m, nitrophenyl)-6-[3- 1H), 7.46(m, 1H), 6.33(s,1H), 4.19-3.81(m, 5H), 2.84(s, (methylamino)pyrrolidin-1- 3H), 2.71(t,2H), 2.57(s, 3H + 1H), 2.34(m, 1H), 1.75(m, yl]pyrimidin-2-amine 2H),1.46(m, 2H), 1.01(t, 3H) dihydrochloride 449 (S)-4-butyl-N-(4-fluoro-3-¹H-NMR(400 MHz, CD₃OD) δ 8.88(m, 1H), 7.72(m,1H), nitrophenyl)-6-[3-7.48(m, 1H), 6.36(s, 1H), 4.16-3.78(m, 5H), 2.83(s, 3H),(methylamino)pyrrolidin-1- 2.70(m, 2H), 2.59(m, 1H), 2.33(m, 1H),1.75(m, 2H), yl]pyrimidin-2-amine 1.46(m, 2H), 1.01(m, 3H)dihydrochloride 450 (S)-4-butyl-N-(4-chloro-3- ¹H-NMR(400 MHz, CD₃OD) δ8.73-8.63(m, 1H), 7.68(m, nitrophenyl)-6-[3- 2H), 6.38(s, 1H),4.19-3.74(m, 5H), 2.84(s, 3H), 2.75(m, (methylamino)pyrrolidin-1- 2H),2.60(m, 1H), 2.36(m, 1H), 1.73(m, 2H), 1.46(m, yl]pyrimidin-2-amine 2H),1.01(m, 3H) dihydrochloride 451 (S)-3-amino-5-{4-butyl-6-[3- ¹H-NMR(400MHz, CD₃OD) δ 7.77-7.74(d, 1H), 7.58(s, (methylamino)pyrrolidin-1- 1H),7.16(s, 1H), 6.35(s, 1H), 4.09-3.77(m, 5H), 2.83(d, yl]pyrimidin-2- 3H),2.72(t, 2H), 2.41(m, 1H), 2.36(m, 1H), 1.74(m, 2H), ylamino}benzonitrile1.02(m, 2H), 0.99(t, 3H) dihydrochloride 452 (S)-N¹-{4-butyl-6-[3-¹H-NMR(400 MHz, CD₃OD) δ 7.89-7.78(d, 1H), 7.54(m,(methylamino)pyrrolidin-1- 1H), 7.17(m, 1H), 6.36(s, 1H), 4.14-3.79(m,5H), 2.83(d, yl]pyrimidin-2-yl}-5- 3H), 2.65(t, 2H), 2.54(m, 1H),2.37(m, 1H), 1.75(m, 2H), (trifluoromethyl)benzene- 1.46(m, 2H), 0.99(t,3H) 1,3-diamine dihydrochloride

TABLE 1-47 Example Compound NMR Spectrum 453 (S)-N¹-{4-butyl-6-[3-¹H-NMR(400 MHz, CD₃OD) δ 7.77(d, 1H), 7.47(m, 1H),(methylamino)pyrrolidin-1- 7.02(t, 1H), 6.27(d, 1H), 4.04-3.75(m, 5H),2.81(d, 3H), yl]pyrimidin-2-yl}-3- 2.58(t, 2H), 2.38(m, 1H), 2.35(m,1H), 1.70(m, 2H), (trifluoromethyl)benzene- 1.45(m, 2H), 0.98(t, 3H)1,4-diamine dihydrochloride 454 (S)-4-butyl-N-[4-fluoro-3- ¹H-NMR(400MHz, CD₃OD) δ 8.13(s, 1H), 7.79(m, 1H), (trifluoromethyl)phenyl]-6-7.40(t, 1H), 6.33(s, 1H), 5.06-3.79(m, 5H), 2.78(s, 3H),[3-(methylamino)pyrrolidin- 2.69(t, 2H), 2.34(m, 1H), 2.27(m, 1H),1.74(m, 2H), 1-yl]pyrimidin-2-amine 1.46(m, 2H), 1.00(t, 3H)dihydrochloride 455 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ8.12(s, 1H), 7.83(m, 1H), (methylamino)pyrrolidin-1- 7.42(t, 1H),4.04-3.82(m, 5H), 2.81(s, 3H), 2.68(t, 2H), yl]pyrimidin-2-ylamino}-2-2.35(m, 1H), 2.32(m, 1H), 1.73(m, 2H), 1.46(m, 2H), fluorobenzonitrile1.00(t, 3H) dihydrochloride 456 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz,CD₃OD) δ 7.49(s, 1H), 7.34(m, 2H), (methylamino)pyrrolidin-1- 6.29(d,1H), 4.11-3.76(m, 5H), 2.82(d, 3H), 2.69(t, 2H), yl]pyrimidin-2-yl}-4-2.60(m, 1H), 2.38(m, 1H), 1.73(m, 2H), 1.45(m, 2H),fluorobenzene-1,3-diamine 0.98(t, 3H) dihydrochloride 457(S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.67(m, 1H), 7.50(m, 1H),(methylamino)pyrrolidin-1- 7.38(m, 1H), 6.33(d, 1H), 4.16-3.77(m, 5H),2.81(d, 3H), yl]pyrimidin-2-yl}-4- 2.69(t, 2H), 2.52(m, 1H), 2.31(m,1H), 1.74(m, 2H), chlorobenzene-1,3-diamine 1.48(m, 2H), 1.00(t, 3H)dihydrochloride 458 (S)-2-amino-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD)δ 7.66(d, 1H), 7.40(m, 1H), (ethylamino)pyrrolidin-1- 6.91(d, 1H),6.24(s, 1H), 4.06-3.70(m, 5H), 3.14(m, 2H), yl]pyrimidin-2- 2.69(m, 2H),2.59-2.56(m, 1H), 2.36(m, 1H), 1.69(m, ylamino}benzonitrile 2H), 1.48(m,2H), 1.37(t, 3H), 0.98(t, 3H) dihydrochloride 459 (S)-3-{4-butyl-6-[3-¹H-NMR(400 MHz, CD₃OD) δ 8.19-8.13(m, 1H), 7.80(m,(ethylamino)pyrrolidin-1- 1H), 7.56(m, 2H), 6.35(s, 1H), 4.07-3.77(m,5H), 3.19(m, yl]pyrimidin-2- 2H), 2.73(t, 2H), 2.60(m, 1H), 2.36(m, 1H),1.75(m, 2H), ylamino}benzonitrile 1.48(m, 2H), 1.37(m, 3H), 0.99(t, 3H)dihydrochloride 460 (S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, DMSO-d₆) δ13.30(brs, 1H), 10.6(brs, (ethylamino)pyrrolidin-1- 1H), 9.53-9.36(m,2H), 8.09(m, 1H), 7.76(m, 1H), yl]pyrimidin-2-ylamino}-2- 7.48(m, 1H),6.34(s, 1H), 3.94(m, 7H), 3.04(m, 2H), methylbenzonitrile 2.62(m, 3H),2.38(m, 2H), 1.70(m, 2H), 1.35(m, 2H), dihydrochloride 0.95(m, 3H),0.91(m, 3H) 461 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ8.76-8.60(m, 1H), 7.38(m, (ethylamino)pyrrolidin-1- 1H), 7.02(m, 1H),6.28(s, 1H), 4.20-3.73(m, 5H), 3.21(m, yl]pyrimidin-2-yl}-3- 2H),2.62(m, 2H), 2.60(m, 1H), 2.25(m, 1H), 1.47(m, nitrobenzene-1,4-diamine2H), 1.40(m, 2H), 1.36(m, 3H), 1.00(m, 3H) dihydrochloride 462(S)-4-butyl-6-[3- ¹H-NMR(400 MHz, DMSO-d₆) δ 13.19(brs, 1H),(ethylamino)pyrrolidin-1-yl]- 10.79(brs, 1H), 9.52-9.38(m, 2H), 8.68(s,1H), 7.67(s, N-(4-methyl-3- 1H), 7.51(m, 1H), 6.35(s, 1H), 3.99-3.63(m,5H), 3.05(m, nitrophenyl)pyrimidin-2- 2H), 2.65(m, 2H), 2.39(m, 2H),1.71(m, 2H), 1.36(m, amine dihydrochloride 2H), 1.27(m, 3H), 0.94(m, 3H)

TABLE 1-48 Example Compound NMR Spectrum 463 (S)-4-butyl-6-[3-¹H-NMR(400 MHz, DMSO-d₆) δ 13.00(brs, 1H), (ethylamino)pyrrolidin-1-yl]-10.77(brs, 1H), 9.34(m, 2H), 8.82(s, 1H), 7.83(s, 1H), N-(4-fluoro-3-7.62(m, 1H), 6.35(s, 1H), 3.93(m, 5H), 3.05(m, 2H),nitrophenyl)pyrimidin-2- 2.65(m, 2H), 2.34(m, 2H), 1.71(m, 2H), 1.37(m,2H), amine dihydrochloride 1.25(m, 3H), 0.94(m, 3H) 464(S)-4-butyl-N-(4-chloro-3- ¹H-NMR(400 MHz, CD₃OD) δ 8.74-8.64(m, 1H),7.68(m, nitrophenyl)-6-[3- 2H), 6.38(s, 1H), 4.18-3.77(m, 5H), 3.22(m,2H), 2.73(m, (ethylamino)pyrrolidin-1- 2H), 2.61(m, 1H), 2.35(m, 1H),1.75(m, 2H), 1.40(m, yl]pyrimidin-2-amine 2H), 1.39(m, 3H), 1.00(m, 3H)dihydrochloride 465 (S)-3-amino-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD)δ 8.17-7.87(m, 2H), 7.39(s, (ethylamino)pyrrolidin-1- 1H), 6.38(d, 1H),4.21-3.78(m, 5H), 3.19(m, 2H), 2.75(m, yl]pyrimidin-2- 2H), 2.59(m, 1H),1.34(m, 1H), 1.76(m, 2H), 1.40(m, ylamino}benzonitrile 2H), 1.39(m, 3H),1.01(m, 3H) dihydrochloride 466 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz,CD₃OD) δ 8.18-8.03(m, 1H), 7.98- (ethylamino)pyrrolidin-1- 7.88(m, 1H),7.40(m, 1H), 6.40(m, 1H), 4.20-3.78(m, yl]pyrimidin-2-yl}-5- 5H),3.20(m, 2H), 2.71(m, 2H), 2.62(m, 1H), 2.31(m, (trifluoromethyl)benzene-1H), 1.75(m, 2H), 1.46(m, 2H), 1.37(m, 3H), 0.99(m, 3H) 1,3-diaminedihydrochloride 467 (S)-N¹-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ8.01-7.89(m, 1H), 7.59(m, (ethylamino)pyrrolidin-1- 1H), 7.20(t, 1H),6.28(d, 1H), 4.08-3.75(m, 5H), 3.21- yl]pyrimidin-2-yl}-3- 3.11(m, 2H),2.69(m, 2H), 2.58-2.52(m, 1H), 2.38- (trifluoromethyl)benzene- 2.27(m,1H), 1.73(m, 2H), 1.45(m, 2H), 1.37(m, 3H), 1,4-diamine dihydrochloride1.00(m, 3H) 468 (S)-4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.16-8.10(m,1H), 7.78(m, (ethylamino)pyrrolidin-1-yl]- 1H), 7.41(m, 1H), 6.33(s,1H), 4.07-3.76(m, 5H), 3.21- N-[4-fluoro-3- 3.19(m, 2H), 2.73(m, 2H),2.56(m, 1H), 2.28(m, 1H), (trifluoromethyl)phenyl]pyrim- 1.72(m, 2H),1.44(m, 2H), 1.36(m, 3H), 1.00(m, 3H) idin-2-amine dihydrochloride 469(S)-5-{4-butyl-6-[3- ¹H-NMR(400 MHz, CD₃OD) δ 8.14(m, 1H), 7.87(m, 1H),(ethylamino)pyrrolidin-1- 7.44(m, 1H), 6.34(s, 1H), 4.08(m, 2H),3.90-3.76(m, 3H), yl]pyrimidin-2-ylamino}-2- 3.19(m, 2H), 2.71(m, 2H),2.59(m, 1H), 2.30(m, 1H), fluorobenzonitrile 1.74(m, 2H), 1.48(m, 2H),1.37(m, 3H), 1.00(m, 3H) dihydrochloride 470 (S)-N¹-{4-butyl-6-[3-¹H-NMR(400 MHz, CD₃OD) δ 7.78-7.72(m, 1H), 7.45(m,(ethylamino)pyrrolidin-1- 1H), 7.35-7.32(m, 1H), 6.31(s, 1H),4.12-3.76(m, 5H), yl]pyrimidin-2-yl}-4- 3.20(m, 2H), 2.72(m, 2H),2.52(m, 1H), 2.30(m, 1H), fluorobenzene-1,3-diamine 1.74(m, 2H), 1.39(m,2H), 1.37(m, 3H), 1.00(m, 3H) dihydrochloride 471 (S)-N¹-{4-butyl-6-[3-¹H-NMR(400 MHz, CD₃OD) δ 7.62(m, 1H), 7.47(m, 1H),(ethylamino)pyrrolidin-1- 7.33(m, 1H), 6.30(s, 1H), 4.17-3.76(m, 5H),3.20(m, 2H), yl]pyrimidin-2-yl}-4- 2.70(m, 2H), 2.40(m, 1H), 2.30(m,1H), 1.74(m, 2H), chlorobenzene-1,3-diamine 1.47(m, 2H), 1.39(m, 3H),1.00(m, 3H) dihydrochloride 472 (S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz,CDCl₃) δ 9.25(brs, NH), 8.27(s, 1H), methylphenylamino)-6- 7.51(d, 1H),7.16(d, 1H), 6.94(brs, NH), 5.67(s, 1H), propylpyrimidin-4- 4.66(m, 1H),4.14(s, 2H), 3.81-3.44(m, 4H), 2.47(m, 5H), yl]pyrrolidin-3-yl}-2-2.33(m, 1H), 2.10(m, 1H), 1.68(m, 2H), 0.98(t, 3H) hydroxyacetamide

TABLE 1-49 Example Compound NMR Spectrum 473 (S)-N-{1-[2-(3-cyano-4-¹H-NMR(400 MHz, CDCl₃) δ 8.29(s, 1H), 7.58(d, 1H), fluorophenylamino)-6-7.10(m, 1H), 6.76(brs, NH), 5.74(s, 1H), 4.67(m, 1H), propylpyrimidin-4-4.14(s, 2H), 3.81-3.42(m, 4H), 2.47(t, 2H), 2.34(m, 1H),yl]pyrrolidin-3-yl}-2- 2.04(m, 1H), 1.72(m, 2H), 0.98(t, 3H)hydroxyacetamide 474 (S)-N-{1-[2-(3-amino-5- ¹H-NMR(400 MHz, CDCl₃) δ7.56(s, NH), 7.10-7.02(m, cyanophenylamino)-6- 2H), 6.69(m, 1H), 6.51(s,1H), 5.73(s, 1H), 4.64(m, 1H), propylpyrimidin-4- 4.14(s, 2H), 3.85(brs,2NH), 3.81-3.49(m, 4H), 2.49(t, yl]pyrrolidin-3-yl}-2- 2H), 2.35(m, 1H),2.06(m, 1H), 1.72(m, 2H), 0.98(t, 3H) hydroxyacetamide 475(S)-N-(1-{2-[3-amino-5- ¹H-NMR(400 MHz, CDCl₃) δ 7.63(s, NH),7.10-6.98(m, (trifluoromethyl)phenylamino]- 2H), 6.78(m, 1H), 6.51(s,1H), 5.68(s, 1H), 4.64(m, 1H), 6-propylpyrimidin-4- 4.13(s, 2H),3.83(brs, 2NH), 3.49(m, 4H), 2.45(t, 2H), yl}pyrrolidin-3-yl)-2- 2.30(m,1H), 2.04(m, 1H), 1.68(m, 2H), 0.96(t, 3H) hydroxyacetamide 476(S)-N-(1-{2-[4-amino-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.11(brs, NH), 7.26(m,2H), (trifluoromethyl)phenylamino]- 6.94(brs, NH), 6.68(m, 1H), 5.63(s,1H), 4.66(m, 1H), 6-propylpyrimidin-4- 4.15(s, 2H), 4.00(brs, 2NH),3.76-3.63(m, 4H), 2.43(t, yl}pyrrolidin-3-yl)-2- 2H), 2.31(m, 1H),2.08(m, 1H), 1.70(m, 2H), 0.96(t, 3H) hydroxyacetamide 477(S)-N-(1-{2-[4-fluoro-3- ¹H-NMR(400 MHz, CDCl₃) δ 8.40(brs, NH), 7.45(m,1H), (trifluoromethyl)phenylamino]- 7.08(m, 2H), 6.70(m, 1H), 5.72(s,1H), 4.66(m, 1H), 6-propylpyrimidin-4- 4.15(s, 2H), 3.78-3.41(m, 4H),2.46(t, 2H), 2.34(m, 1H), yl}pyrrolidin-3-yl)-2- 2.04(m, 1H), 1.70(m,2H), 0.97(t, 3H) hydroxyacetamide 478 (S)-N-{1-[2-(3-amino-4- ¹H-NMR(400MHz, CDCl₃) δ 7.21(m, 1H), 6.86(m, 2H), fluorophenylamino)-6- 6.80(brs,NH), 5.64(s, 1H), 4.64(m, 1H), 4.15(s, 2H), propylpyrimidin-4- 3.76(brs,2NH), 3.63-3.59(m, 4H), 2.44(t, 2H), 2.31(m, yl]pyrrolidin-3-yl}-2- 1H),2.05(m, 1H), 1.70(m, 2H), 0.97(t, 3H) hydroxyacetamide 479(S)-N-{1-[2-(3-amino-4- ¹H-NMR(400 MHz, CD₃OD) δ 7.25(s, 1H), 7.06(m,1H), chlorophenylamino)-6- 6.92(m, 1H), 5.89(s, 1H), 4.55(m, 1H),3.99(s, 2H), 3.87- propylpyrimidin-4- 3.62(m, 4H), 2.49(t, 2H), 2.31(m,1H), 2.10(m, 1H), yl]pyrrolidin-3-yl}-2- 1.71(m, 2H), 0.99(t, 3H)hydroxyacetamide 480 (S)-N-{1-[2-(3-chloro-4- ¹H-NMR(400 MHz, CDCl₃) δ7.96(brs, NH), 7.21(m, 1H), methylphenylamino)-6- 7.09(m, 1H), 6.92(brs,NH), 6.76(m, 1H), 5.67(s, 1H), propylpyrimidin-4- 4.67(m, 1H), 4.14(s,2H), 3.77-3.43(m, 4H), 2.45(t, 2H), yl]pyrrolidin-3-yl}-2- 2.31(m, 4H),2.04(m, 1H), 1.69(m, 2H), 0.97(t, 3H) hydroxyacetamide 481(S)-2-hydroxy-N-(1-{2-[4- ¹H-NMR(400 MHz, CDCl₃) δ 8.36(brs, NH),7.38(m, 1H), methyl-3- 7.16(m, 2H), 6.78(m, 1H), 5.67(s, 1H), 4.66(m,1H), (trifluoromethyl)phenylamino]- 4.14(s, 2H), 3.76-3.61(m, 4H),2.47(m, 5H), 2.30(m, 1H), 6-propylpyrimidin-4- 2.04(m, 1H), 1.70(m, 2H),0.96(t, 3H) yl}pyrrolidin-3-yl)acetamide

TABLE 1-50 Example Compound NMR Spectrum 482 (S)-N-{1-[2-(3-amino-5-¹H-NMR(400 MHz, CD₃OD) δ 7.73(m, 2H), 7.22(d, 1H), cyanophenylamino)-6-6.31(d, 1H), 4.57(m, 1H), 4.05(s, 2H), 3.95-3.54(m, 4H),propylpyrimidin-4- 2.67(m, 2H), 2.38(m, 1H), 2.19(m, 2H), 1.80(m, 2H),yl]pyrrolidin-3-yl}-2- 1.05(m, 3H) hydroxyacetamide hydrochloride 483(S)-N-{1-[2-(3-cyano-4- ¹H-NMR(400 MHz, CD₃OD) δ 8.02(d, 1H), 7.71(m,1H), methylphenylamino)-6- 7.43(d, 1H), 6.27(d, 1H), 4.56(m, 1H),3.99(s, 2H), 3.90- propylpyrimidin-4- 3.47(m, 4H), 2.64(m, 2H), 2.52(s,3H), 2.17(m, 1H), yl]pyrrolidin-3-yl}-2- 2.01(m, 1H), 1.78(m, 2H),1.05(m, 3H) hydroxyacetamide hydrochloride 484 (S)-4-fluoro-N¹-{4-[3-¹H-NMR(400 MHz, CD₃OD) δ 7.67-7.62(m, 1H), 7.44-(methylamino)pyrrolidin-1- 7.28(m, 2H), 6.30(d, 1H), 4.12-3.76(m, 5H),2.81(d, 3H), yl]-6-propylpyrimidin-2- 2.67(dd, 2H), 2.60-2.01(m, 2H),1.82-1.62(m, 2H), 1.05(t, yl}benzene-1,3-diamine 3H) dihydrochloride 485(S)-3-amino-5-({4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.79(d, 1H), 7.67(d, 1H),(methylamino)pyrrolidin-1- 7.21(s, 1H), 6.36(d, 1H), 4.19-3.77(m, 5H),2.82(d, 3H), yl]-6-propylpyrimidin-2- 2.70(dd, 2H), 2.64-2.36(m, 2H),1.84-1.77(m, 2H), 1.05(t, yl}amino)benzonitrile 3H) dihydrochloride 486(S)-2-amino-5-({4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.63-7.62(m, 1H), 7.43-(methylamino)pyrrolidin-1- 7.39(m, 1H), 6.90(d, 1H), 6.24(d, 1H),4.12-3.73(m, 5H), yl]-6-propylpyrimidin-2- 2.79(d, 3H), 2.64(dd, 2H),2.59-2.25(m, 2H), 1.79- yl}amino)benzonitrile 1.73(m, 2H), 1.04(t, 3H)dihydrochloride 487 (S)-N¹-{4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.74(d, 1H),7.47(d, 1H), (methylamino)pyrrolidin-1- 7.10(s, 1H), 6.35(s, 1H),4.20-3.70(m, 5H), 2.81(d, 3H), yl]-6-propylpyrimidin-2-yl}-5- 2.69(t,2H), 2.69-2.50(m, 1H), 2.45-2.25(m, 1H), 1.90- (trifluoromethyl)benzene-1.70(m, 2H), 1.06(t, 3H) 1,3-diamine dihydrochloride 488 (S)-N¹-{4-[3-¹H-NMR(400 MHz, CD₃OD) δ 7.79(d, 1H), 7.50-7.40(m,(ethylamino)pyrrolidin-1-yl]- 1H), 7.02(t, 1H), 6.30-6.20(m, 1H),4.20-3.60(m, 5H), 6-propylpyrimidin-2-yl}-3- 3.25-3.00(m, 2H), 2.65(t,2H), 2.60-2.40(m, 1H), 2.40- (trifluoromethyl)benzene- 2.20(m, 1H),1.78(q, 2H), 1.40-1.30(m, 3H), 1.05(t, 3H) 1,4-diamine dihydrochloride489 (S)-2-amino-5-({4-[3- ¹H-NMR(400 MHz, CD₃OD) δ 7.69(d, 1H),7.55-7.45(m, (ethylamino)pyrrolidin-1-yl]- 1H), 6.96(d, 1H), 6.25(d,1H), 4.15-3.60(m, 5H), 3.25- 6-propylpyrimidin-2- 3.05(m, 2H), 2.65(t,2H), 2.65-2.45(m, 1H), 2.40-2.20(m, yl}amino)benzonitrile 1H), 1.75(q,2H), 1.37(t, 3H), 1.04(t, 3H) dihydrochloride 490 (S)-N-[4-fluoro-3-¹H-NMR(400 MHz, CD₃OD) δ 8.47(d, 1H), 7.75-7.65(m,(trifluoromethyl)phenyl]-4- 1H), 7.20(t, 1H), 5.97(s, 1H), 4.00-3.85(m,2H), 3.85- [3-(methylamino)pyrrolidin- 3.50(m, 3H), 2.78(s, 3H),2.60-2.40(m, 3H), 2.30-2.20(m, 1-yl]-6-propylpyrimidin-2- 1H), 1.74(q,2H), 0.98(t, 3H) amine hydrochloride

TABLE 1-51 Example Compound NMR Spectrum 491 (S)-4-[3- ¹H-NMR(400 MHz,CD₃OD) δ 8.45(d, 1H), 7.71(d, 1H), (ethylamino)pyrrolidin-1-yl]- 7.20(t,1H), 5.97(s, 1H), 4.10-3.85(m, 2H), 3.85-3.50(m, N-[4-fluoro-3- 3H),3.16(t, 2H), 2.60-2.40(m, 3H), 2.30-2.15(m, 1H),(trifluoromethyl)phenyl]-6- 1.75(q, 2H), 1.36(t, 3H), 0.98(t, 3H)propylpyrimidin-2-amine hydrochloride 492 (S)-N-{1-[6-butyl-2-(3-¹H-NMR(400 MHz, CD₃OD) δ 7.97(d, 1H), 7.71(t, 1H), cyano-4- 7.44(d, 1H),6.24(d, 1H), 4.48(d, 1H), 4.00-3.40(m, 4H), methylphenylamino)pyrimidin-2.67(t, 2H), 2.52(s, 3H), 2.40-2.20(m, 1H), 2.15-2.00(m,4-yl]pyrrolidin-3- 1H), 1.95(s, 3H), 1.80-1.60(m, 2H), 1.45(q, 2H),0.98(t, yl}acetamide hydrochloride 3H) 493 (S)-N-{1-[2-(3-amino-4-¹H-NMR(400 MHz, CD₃OD) δ 7.00(d, 1H), 6.92(s, 1H), methylphenylamino)-6-6.76(t, 1H), 6.14(d, 1H), 4.47(d, 1H), 4.00-3.35(m, 4H),propylpyrimidin-4- 2.60(t, 2H), 2.40-2.20(m, 1H), 2.13(s, 3H),2.15-2.00(m, yl]pyrrolidin-3-yl}acetamide 1H), 1.95(s, 3H), 1.74(q, 2H),1.03(t, 3H) hydrochloride 494 (S)-N-(1-{2-[(3,4- ¹H-NMR(400 MHz, CD₃OD)δ 6.88(s, 1H), 6.70(m, 2H), diaminophenyl)amino]-6- 6.02(s, 1H),4.45(brs, 1H), 3.83-3.63(m, 3H), 2.55(m, propylpyrimidin-4- 2H),2.28(br, 1H), 2.03(br, 1H), 1.97(s, 3H), 1.72(m, 2H),yl}pyrrolidin-3-yl)acetamide 1.01(t, 3H)

Test Example 1: Evaluation of Agonistic Activity in CHO-K1 CellsExpressing Human 5-HT_(4(a))

As CHO-K1 cells stably expressing human 5-HT_(4(a)), we used theGeneBIAzer HTR4-CRE-bla CHO-K1 cells (Invitrogen Corp.). The cells werecultured, under the condition of 37

and 5% CO₂, in a DMEM supplemented with 10% fetal bovine serum (FBS), 25mM HEPES (pH7.4), 600 μg/ml hygromycin B, 0.1 mM non-essential aminoacids, 100 unit/ml penicillin and 100 μg/ml streptomycin. Subcultureswere performed three times per one week, each being at less than 80%confluence. At the previous day before treating test compounds, thecells were collected using 0.5% trypsin/EDTA and then diluted with aDMEM supplemented with 1% FBS, 25 mM HEPES, and 0.1 mM non-essentialamino acids into 3.125×10⁵ cells/ml. 32 μl of the diluted cells wereadded into 384-well plate (10⁴ cells per well) and then incubatedovernight. After the overnight culture, 8 μl of the medium having 1% ofDMSO was added into the cell-free control well and the non-stimulatingcontrol well, respectively. 8 μl of the respective test compounddilutions (which had been prepared by diluting by 100-times with themedium as mentioned in the above) having 1% of DMSO were added to therespective remaining wells. After being cultured in the incubator for 5hours, the wells of the 384-plate were treated with the substratesolution (8 μl per well) prepared according to the vendor's instruction(i.e., Invitrogen's instruction), and then incubated in the dark roomfor additional two hours. Agonistic activities on 5-HT₄ receptor wereevaluated, on the basis of fluorescence values of the cleavage-productsby beta-lactamase. After exciting to 410 nm of wavelength using afluorescence detector (Genios Pro), we measured the fluorescence valuesat two emission wavelengths (first wavelength: 465 nm, secondwavelength: 535 nm). Data were analyzed on the basis of the ratio offluorescence intensities of each well at the respective wavelengths.Each EC₅₀ value was calculated by non-linear regression analysis usingthe “GraphPad Prism” program, based on the activities according to8-different concentrations of the test compounds. The results are shownin Table 2-1 to 2-3 below.

TABLE 2-1 Example EC₅₀(nM) 13 0.12 17 0.35 18 0.14 22 0.33 31 0.13 320.23 33 0.059 34 0.16 36 0.243 40 0.03 41 0.15 42 0.033 43 0.178 440.022 45 0.036 46 0.0097 47 0.38 50 0.012 52 0.33 53 0.098 54 0.032 550.016 56 0.312 57 0.389 59 0.028 60 0.047 61 0.15 62 0.36 63 0.13 66 0.167 0.19 71 0.25 73 0.27 75 0.22 77 0.15 78 0.28 79 0.44 80 0.17 81 0.20582 0.048 84 0.031 85 0.003 86 0.039 87 0.048 88 0.041 89 0.08 90 0.09191 0.014 92 0.057 93 0.01 94 0.041 95 0.081 96 0.017 97 0.046 98 0.09499 0.0015 100 0.31 102 0.39 103 0.067 104 0.073 105 0.005 106 0.13 1070.42 108 0.21 109 0.012 110 0.018 111 0.008 112 0.045 113 0.016 1160.0035 117 0.014 121 0.005 123 0.0019 125 0.159 127 0.0062 128 0.039 1290.323 131 0.091 133 0.039 134 0.214 135 0.011 136 0.045 137 0.072 1380.012 139 0.034 140 0.028 141 0.085 142 0.01 143 0.0066 144 0.036 1450.046 146 0.084 149 0.277 150 0.41 151 0.334 153 0.228 155 0.417 1560.219 157 0.044 158 0.436 160 0.121 161 0.119 162 0.193 165 0.2 1660.103 170 0.0013 171 0.00064 173 0.004 175 0.229 176 0.018 177 0.02 1800.0087 181 0.00088 182 0.036 185 0.015 186 0.382 187 0.037 189 0.028 1900.05 191 0.29 192 0.02 194 0.2 195 0.25 196 0.1 203 0.3 204 0.47 2060.16 207 0.083 208 0.06 210 0.016 211 0.019 212 0.0089 213 0.017 2140.029 215 0.018 217 0.23 220 0.07 221 0.149 222 0.082 223 0.011 2240.0043 225 0.052 226 0.052 228 0.014

TABLE 2-2 Example EC₅₀(nM) 229 0.00098 230 0.047 231 0.0067 232 0.13 2330.019 234 0.0012 235 0.0023 236 0.209 237 0.0013 238 0.00039 239 0.115240 0.0025 241 0.012 242 0.058 243 0.011 244 0.028 245 0.053 246 0.04247 0.012 248 0.016 249 0.0018 251 0.01 252 0.0052 253 0.014 254 0.0015255 0.023 260 0.015 261 0.0071 262 0.0039 268 0.011 270 0.204 274 0.087279 0.078 280 0.026 281 0.196 282 0.103 286 0.0047 289 0.062 290 0.013291 0.0074 292 0.038 293 0.0043 294 0.076 295 0.048 296 0.039 297 0.028301 0.11 302 0.42 303 0.12 304 0.07 305 0.18 307 0.24 309 0.076 310 0.37311 0.019 312 0.023 313 0.078 314 0.18 315 0.028 316 0.21 317 0.14 3180.16 319 0.08 320 0.041 321 0.044 322 0.15 323 0.027 325 0.085 326 0.028327 0.025 328 0.017 329 0.18 331 0.138 332 0.046 333 0.024 334 0.085 3370.0026 338 0.0032 342 0.0055 344 0.0092 345 0.062 346 0.014 347 0.03 3480.019 349 0.016 350 0.012 351 0.0035 352 0.0027 353 0.01 354 0.003 3550.007 357 0.0065 358 0.014 359 0.0021 362 0.0021 364 0.122 365 0.027 3660.078 367 0.153 368 0.182 369 0.049 370 0.015 372 0.0046 373 0.0043 3740.0027 375 0.0033 376 0.0037 377 0.0013 378 0.015 379 0.0098 380 0.009381 0.0043 382 0.0051 383 0.0057 384 0.077 387 0.007 395 0.082 399 0.13400 0.033 401 0.073 402 0.236 403 0.414 405 0.399 406 0.402 407 0.254414 0.0034 415 0.015 416 0.0074 417 0.0051 418 0.0022 419 0.0032 4200.0029 421 0.0079 422 0.011 423 0.0084 424 0.02 425 0.056 426 0.079 4270.024 428 0.066 429 0.025 430 0.027 431 0.029 433 0.055

TABLE 2-3 Example EC₅₀(nM) 434 0.111 436 0.01 437 0.02 438 0.015 4390.0075 440 0.017 441 0.0095 442 0.041 443 0.0099 444 0.012 445 0.0098446 0.0077 447 0.0023 448 0.0025 449 0.0044 450 0.0078 451 0.003 4520.0033 453 0.0016 454 0.014 455 0.0038 456 0.0026 457 0.003 458 0.0017459 0.0034 460 0.0019 461 0.0019 462 0.0026 463 0.0021 464 0.0039 4650.0022 466 0.0058 467 0.0014 468 0.0062 469 0.0021 470 0.0025 471 0.0033472 0.0075 473 0.022 474 0.0066 475 0.011 476 0.014 477 0.0096 478 0.024479 0.0064 480 0.032 481 0.0093 484 0.0058 485 0.0024 486 0.0014 4870.0021 488 0.00077 489 0.0015 490 0.0048 491 0.0029 492 0.019 493 0.024

As shown in Table 2-1 to 2-3, the compounds of the present inventionhave excellent activities as a 5-HT₄ receptor agonist, and thereforethey can be usefully applied for preventing or treating the dysfunctionin gastrointestinal motility.

1. A compound of Formula 1 or its pharmaceutically acceptable salt:

wherein, R₁ is a phenyl group substituted with one or more substituentsselected from the group consisting of hydroxy, amino, halogen, cyano,nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or aheteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or anoxo(═O) group, R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; aphenoxy group; a benzyloxy group; a C₁₋₅ alkyl group optionallysubstituted with a substituent selected from the group consisting ofamino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or agroup selected from the group consisting of the following Formulas A toE (where * in Formulas A to E represents the position attached to thecompounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionallysubstituted with hydroxy, R₅ is a C₁₋₅ alkyl group optionallysubstituted with phenyl; or a C₂₋₆ alkenyl group optionally substitutedwith phenyl or C₃₋₆ cycloalkyl, R₆ is a C₁₋₁₀ alkyl group optionallysubstituted with a substituent selected from the group consisting ofhydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino,benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionallysubstituted with one or more substituents selected from the groupconsisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl,pyridinyl, indolyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl,triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, piperidinyl,piperazinyl (where the piperazinyl is optionally substituted withbenzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group;a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; aC₁₋₁₀ alkenyl group optionally substituted with phenyl; atrifluoromethyl group; a trifluoroethyl group; or a phenyl groupoptionally substituted with halogen, R₇ is hydrogen; or a C₁₋₅ alkylgroup, R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkylgroup optionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.
 2. The compound or its pharmaceuticallyacceptable salt of claim 2, wherein R₁ is a phenyl group substitutedwith one or more substituents selected from the group consisting ofhydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl, C₁₋₅ alkyl(where the C₁₋₅ alkyl is optionally substituted with halogen or amino),C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substituted withhalogen), C₁₋₅ alkylthio, aminosulfonyl, aminocarbonyl, C₁₋₅alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl groupselected from the group consisting of quinolinyl, chromenonyl, indolyl,indolinyl, and benzimidazolyl, wherein the heteroaryl group may beoptionally substituted with one or more substituents selected from thegroup consisting of C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen) and acetyl, R₂ is hydrogen; a C₁₋₅ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of hydroxyl and C₁₋₅ alkoxy, benzylamino (where thebenzylamino is optionally substituted with halogen), phenylamino, C₁₋₅alkylamino, C₃₋₆ cycloalkylamino, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅alkoxycarbonyl group; or a formyl group, R₃ is hydrogen; a hydroxylgroup; a C₁₋₅ alkyl group optionally substituted with a substituentselected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino,and mono- or di-C₁₋₅ alkylamino; or a group selected from the groupconsisting of the Formulas A, B, D and E, R₄ is hydrogen, R₅ is a C₁₋₅alkyl group, R₆ is a C₁₋₁₀ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, halogen, C₁₋₅alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono-or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl,piperazinyl (where the piperazinyl is optionally substituted withbenzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group;a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; aC₁₋₁₀ alkenyl group optionally substituted with phenyl; atrifluoromethyl group; a trifluoroethyl group; or a phenyl groupoptionally substituted with halogen, R₇ is hydrogen, R₈ and R₉ are,independently each other, hydrogen; a C₁₋₁₀ alkyl group optionallysubstituted with a substituent selected from the group consisting ofamino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀cycloalkyl, phenyl (where the phenyl is optionally substituted with oneor more substituents selected from the group consisting of hydroxy, C₁₋₅alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (wherethe furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl),pyridinyl, and benzyloxy; a piperidinyl group optionally substitutedwith benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinylgroup optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety isoptionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.
 3. Apharmaceutical composition for agonizing a 5-HT₄ receptor, comprising atherapeutically effective amount of a compound of Formula 1 or itspharmaceutically acceptable salt; and a pharmaceutically acceptablecarrier

wherein, R₁ is a phenyl group substituted with one or more substituentsselected from the group consisting of hydroxy, amino, halogen, cyano,nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or aheteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or anoxo(═O) group, R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; aphenoxy group; a benzyloxy group; a C₁₋₅ alkyl group optionallysubstituted with a substituent selected from the group consisting ofamino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or agroup selected from the group consisting of the following Formulas A toE (where * in Formulas A to E represents the position attached to thecompounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionallysubstituted with hydroxy, R₅ is a C₁₋₅ alkyl group optionallysubstituted with phenyl; or a C₂₋₆ alkenyl group optionally substitutedwith phenyl or C₃₋₆ cycloalkyl, R₆ is a C₁₋₁₀ alkyl group optionallysubstituted with a substituent selected from the group consisting ofhydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino,benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionallysubstituted with one or more substituents selected from the groupconsisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl,pyridinyl, indolyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl,triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, piperidinyl,piperazinyl (where the piperazinyl is optionally substituted withbenzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group;a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; aC₁₋₁₀ alkenyl group optionally substituted with phenyl; atrifluoromethyl group; a trifluoroethyl group; or a phenyl groupoptionally substituted with halogen, R₇ is hydrogen; or a C₁₋₅ alkylgroup, R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkylgroup optionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group, wherein the agonizing a 5-HT₄ receptoreffects to treat a dysfunction in gastrointestinal motility in a diseaseselected from the group consisting of gastroesophageal reflux disease(GERD), constipation, irritable bowel syndrome (IBS), dyspepsia,post-operative ileus, delayed gastric emptying, gastroparesis,intestinal pseudo-obstruction, drug-induced delayed transit, anddiabetic gastric atony.
 4. The pharmaceutical composition of claim 3,wherein R₁ is a phenyl group substituted with one or more substituentsselected from the group consisting of hydroxy, amino, halogen, cyano,nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), C₁₋₅ alkylthio, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or aheteroaryl group selected from the group consisting of quinolinyl,chromenonyl, indolyl, indolinyl, and benzimidazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of C₁₋₅ alkyl (where theC₁₋₅ alkyl is optionally substituted with halogen) and acetyl, R₂ ishydrogen; a C₁₋₅ alkyl group optionally substituted with a substituentselected from the group consisting of hydroxyl and C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino, andhydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group; or a formyl group,R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkyl group optionallysubstituted with a substituent selected from the group consisting ofamino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or agroup selected from the group consisting of the Formulas A, B, D and E,R₄ is hydrogen, R₅ is a C₁₋₅ alkyl group, R₆ is a C₁₋₁₀ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of hydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅alkoxycarbonylamino, benzyloxycarbonylamino, mono- or di-C₁₋₅alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy, phenyl (wherethe phenyl is optionally substituted with one or more substituentsselected from the group consisting of halogen, amino, C₁₋₅ alkoxy, andhydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl, piperazinyl(where the piperazinyl is optionally substituted with benzyl), C₃₋₆cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group; a piperidinylgroup optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₁₀ alkenylgroup optionally substituted with phenyl; a trifluoromethyl group; atrifluoroethyl group; or a phenyl group optionally substituted withhalogen, R₇ is hydrogen, R₈ and R₉ are, independently each other,hydrogen; a C₁₋₁₀ alkyl group optionally substituted with a substituentselected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino,hydroxy, C₁₋₅ alkylthio, C₃₋₁₀ cycloalkyl, phenyl (where the phenyl isoptionally substituted with one or more substituents selected from thegroup consisting of hydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino,trifluoromethyl, halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy),thiophenyl, pyrrolyl, furanyl (where the furanyl is optionallysubstituted with mono- or di-C₁₋₅ alkyl), pyridinyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group.
 5. A method for agonizing a 5-HT₄ receptor,comprising administering an effective amount of a compound of Formula 1or a pharmaceutically acceptable salt thereof to a subject in needthereof:

wherein, R₁ is a phenyl group substituted with one or more substituentsselected from the group consisting of hydroxy, amino, halogen, cyano,nitro, hydroxycarbonyl, C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen or amino), C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₅alkoxy (where the C₁₋₅ alkoxy is optionally substituted with halogen),C₁₋₅ alkylthio, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkylsulfonylamino,C₁₋₅ alkylcarbonylamino, C₁₋₅ alkoxycarbonyl, aminosulfonyl,aminocarbonyl, C₁₋₅ alkylaminocarbonyl, and benzyloxycarbonylamino; or aheteroaryl group selected from the group consisting of pyridinyl,pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl,thiazolyl, furanyl, pyrrolyl, thiophenyl, naphthyl, indanyl, quinolinyl,quinolinonyl, chromenonyl, dihydroindolonyl, isoindoline-1,3-dionyl,dihydrobenzimidazolonyl, benzoxazolonyl, benzofuranyl, benzothiophenyl,benzo[d][1,3]dioxolyl, dihydrobenzo[1,4]dioxinyl, indolyl, indolinyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, and indazolyl, wherein theheteroaryl group may be optionally substituted with one or moresubstituents selected from the group consisting of amino, di-C₁₋₅alkylamino, cyano, nitro, halogen, C₁₋₅ alkyl (where the C₁₋₅ alkyl isoptionally substituted with halogen), C₁₋₅ alkoxy (where the C₁₋₅ alkoxyis optionally substituted with halogen), acetyl, and C₁₋₅ alkylsulfonyl,R₂ is hydrogen; a C₁₋₅ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, C₁₋₅ alkoxy,benzylamino (where the benzylamino is optionally substituted withhalogen), phenylamino, C₁₋₅ alkylamino, C₃₋₆ cycloalkylamino,pyrrolidinyl, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅ alkoxycarbonyl group;a hydroxycarbonyl group; an aminocarbonyl group; a formyl group; or anoxo(═O) group, R₃ is hydrogen; a hydroxyl group; a C₁₋₅ alkoxy group; aphenoxy group; a benzyloxy group; a C₁₋₅ alkyl group optionallysubstituted with a substituent selected from the group consisting ofamino, C₁₋₅ alkoxycarbonylamino, and mono- or di-C₁₋₅ alkylamino; or agroup selected from the group consisting of the following Formulas A toE (where * in Formulas A to E represents the position attached to thecompounds of Formula 1),

R₄ is hydrogen; a hydroxyl group; or a C₁₋₅ alkyl group optionallysubstituted with hydroxy, R₅ is a C₁₋₅ alkyl group optionallysubstituted with phenyl; or a C₂₋₆ alkenyl group optionally substitutedwith phenyl or C₃₋₆ cycloalkyl, R₆ is a C₁₋₁₀ alkyl group optionallysubstituted with a substituent selected from the group consisting ofhydroxy, halogen, C₁₋₅ alkoxy, amino, C₁₋₅ alkoxycarbonylamino,benzyloxycarbonylamino, mono- or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅alkyloxy, phenoxy, benzyloxy, phenyl (where the phenyl is optionallysubstituted with one or more substituents selected from the groupconsisting of halogen, amino, C₁₋₅ alkoxy, and hydroxy), thiophenyl,pyridinyl, indolyl, pyrimidinyl, pyrazinyl, imidazolyl, pyrazolyl,triazolyl, oxazolyl, thiazolyl, furanyl, pyrrolyl, piperidinyl,piperazinyl (where the piperazinyl is optionally substituted withbenzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group;a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; aC₁₋₁₀ alkenyl group optionally substituted with phenyl; atrifluoromethyl group; a trifluoroethyl group; or a phenyl groupoptionally substituted with halogen, R₇ is hydrogen; or a C₁₋₅ alkylgroup, R₈ and R₉ are, independently each other, hydrogen; a C₁₋₁₀ alkylgroup optionally substituted with a substituent selected from the groupconsisting of amino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio,C₃₋₁₀ cycloalkyl, phenyl (where the phenyl is optionally substitutedwith one or more substituents selected from the group consisting ofhydroxy, C₁₋₅ alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl,halogen, C₁₋₅ alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl,furanyl (where the furanyl is optionally substituted with mono- ordi-C₁₋₅ alkyl), pyridinyl, pyrimidinyl, pyrazinyl, imidazolyl,pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, and benzyloxy; apiperidinyl group optionally substituted with benzyl, benzoyl, C₁₋₅alkyl, or C₁₋₅ alkylcarbonyl; an azetidinyl group optionally substitutedwith C₁₋₅ alkoxycarbonyl; a C₁₋₅ alkylsulfonyl group; a phenylsulfonylgroup (where the phenyl moiety is optionally substituted with halogen);or a C₃₋₁₀ cycloalkyl group, wherein the agonizing a 5-HT₄ receptoreffects to treat a dysfunction in gastrointestinal motility in a diseaseselected from the group consisting of gastroesophageal reflux disease(GERD), constipation, irritable bowel syndrome (IBS), dyspepsia,post-operative ileus, delayed gastric emptying, gastroparesis,intestinal pseudo-obstruction, drug-induced delayed transit, anddiabetic gastric atony.
 6. The method of claim 5, wherein R₁ is a phenylgroup substituted with one or more substituents selected from the groupconsisting of hydroxy, amino, halogen, cyano, nitro, hydroxycarbonyl,C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionally substituted with halogenor amino), C₁₋₅ alkoxy (where the C₁₋₅ alkoxy is optionally substitutedwith halogen), C₁₋₅ alkylthio, aminosulfonyl, aminocarbonyl, C₁₋₅alkylaminocarbonyl, and benzyloxycarbonylamino; or a heteroaryl groupselected from the group consisting of quinolinyl, chromenonyl, indolyl,indolinyl, and benzimidazolyl, wherein the heteroaryl group may beoptionally substituted with one or more substituents selected from thegroup consisting of C₁₋₅ alkyl (where the C₁₋₅ alkyl is optionallysubstituted with halogen) and acetyl, R₂ is hydrogen; a C₁₋₅ alkyl groupoptionally substituted with a substituent selected from the groupconsisting of hydroxyl and C₁₋₅ alkoxy, benzylamino (where thebenzylamino is optionally substituted with halogen), phenylamino, C₁₋₅alkylamino, C₃₋₆ cycloalkylamino, and hydroxy-C₁₋₅ alkylamino; a C₁₋₅alkoxycarbonyl group; or a formyl group, R₃ is hydrogen; a hydroxylgroup; a C₁₋₅ alkyl group optionally substituted with a substituentselected from the group consisting of amino, C₁₋₅ alkoxycarbonylamino,and mono- or di-C₁₋₅ alkylamino; or a group selected from the groupconsisting of the Formulas A, B, D and E, R₄ is hydrogen, R₅ is a C₁₋₅alkyl group, R₆ is a C₁₋₁₀ alkyl group optionally substituted with asubstituent selected from the group consisting of hydroxy, halogen, C₁₋₅alkoxy, amino, C₁₋₅ alkoxycarbonylamino, benzyloxycarbonylamino, mono-or di-C₁₋₅ alkylamino, C₁₋₅ alkoxy-C₁₋₅ alkyloxy, phenoxy, benzyloxy,phenyl (where the phenyl is optionally substituted with one or moresubstituents selected from the group consisting of halogen, amino, C₁₋₅alkoxy, and hydroxy), thiophenyl, pyridinyl, indolyl, piperidinyl,piperazinyl (where the piperazinyl is optionally substituted withbenzyl), C₃₋₆ cycloalkyl, acetyl, and benzoyl; a C₃₋₆ cycloalkyl group;a piperidinyl group optionally substituted with C₁₋₅ alkoxycarbonyl; aC₁₋₁₀ alkenyl group optionally substituted with phenyl; atrifluoromethyl group; a trifluoroethyl group; or a phenyl groupoptionally substituted with halogen, R₇ is hydrogen, R₈ and R₉ are,independently each other, hydrogen; a C₁₋₁₀ alkyl group optionallysubstituted with a substituent selected from the group consisting ofamino, C₁₋₅ alkoxycarbonylamino, hydroxy, C₁₋₅ alkylthio, C₃₋₁₀cycloalkyl, phenyl (where the phenyl is optionally substituted with oneor more substituents selected from the group consisting of hydroxy, C₁₋₅alkyl, mono- or di-C₁₋₅ alkylamino, trifluoromethyl, halogen, C₁₋₅alkoxy, and C₁₋₅ alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (wherethe furanyl is optionally substituted with mono- or di-C₁₋₅ alkyl),pyridinyl, and benzyloxy; a piperidinyl group optionally substitutedwith benzyl, benzoyl, C₁₋₅ alkyl, or C₁₋₅ alkylcarbonyl; an azetidinylgroup optionally substituted with C₁₋₅ alkoxycarbonyl; a C₁₋₅alkylsulfonyl group; a phenylsulfonyl group (where the phenyl moiety isoptionally substituted with halogen); or a C₃₋₁₀ cycloalkyl group.